KR102557818B1 - Chimeric poxvirus composition and use thereof - Google Patents

Abstract

Provided herein are particularly viral compositions and methods of use thereof. Provided viral compositions are particularly useful in methods of treating cancer comprising a therapeutically effective amount of a chimeric poxvirus. A chimeric poxvirus provided herein may further comprise a transgene.

Description

Chimeric poxvirus composition and use thereof

CROSS REFERENCES OF RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No. 62/372,408, filed on August 9, 2016, and U.S. Provisional Application No. 62/519,010, filed on June 13, 2017, which is hereby incorporated by reference in its entirety for all purposes. included as

Statement Regarding a "Sequence Listing", Table, or Computer Program Listing Supplement Submitted as an ASCII File

The Sequence Listing compiled in file 48440-606001WO_ST25, created on August 8, 2017 on a machine format IBM-PC, MS-Windows operating system of 696,239 bytes, is hereby incorporated by reference.

Cancer is the second leading cause of death in the United States. In recent years, significant advances have been made in cancer immunotherapy, including immune checkpoints, T cells with chimeric antigen receptors, and oncolytic viruses. Oncolytic viruses are naturally occurring or genetically modified viruses that infect cancer cells, replicate within them, and eventually kill cancer cells without damaging healthy cells. However, the clinical benefit of oncolytic viruses as a monotherapy is still limited. There is a need in the art for new compositions that exploit the advantageous characteristics of oncolytic viruses while maximizing safety and clinical outcomes. In particular, solutions to these and other problems in the art are disclosed herein.

Brief summary of the invention

In one aspect, a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, wherein the nucleic acid sequence is a vaccinia virus strain Brighton, raccoonpox Virus strain Herman, rabbitpox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia virus Nucleic acid fragments from two or more poxvirus strains selected from the group comprising strain Lederle-Chorioallantoic, vaccinia virus strain AS, orf virus strain NZ2 and pseudocowpox virus strain TJS. A chimeric poxvirus comprising a is provided.

In one aspect, an isolated nucleic acid encoding a chimeric poxvirus described herein is provided.

In one aspect, a pharmaceutical composition comprising a therapeutically effective amount of a chimeric poxvirus described herein is provided.

In another aspect, a method of treating cancer in a subject in need thereof is provided, comprising treating the cancer in a subject by administering to the subject a therapeutically effective amount of a chimeric poxvirus described herein. In an embodiment, the cancer is breast cancer, colon cancer, kidney cancer, leukemia, lung cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer, brain cancer, liver cancer, stomach cancer, or sarcoma.

In another embodiment, a method for forming a chimeric poxvirus is provided, comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia Infecting a cell with two or more poxvirus strains selected from the group consisting of vaccinia virus strain CL, vaccinia virus strain Ledle-Yoran, vaccinia virus strain AS, sheeppox virus strain NZ2 and pseudovax virus strain TJS; and allowing two or more poxvirus strains to replicate to form a chimeric poxvirus.

In one aspect, a method of inhibiting cell proliferation of a cell is provided, comprising contacting the cell with a chimeric poxvirus described herein.

In one embodiment, a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, wherein the nucleic acid sequence is vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, Vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Elora, vaccinia virus strain AS, sheeppox virus strain NZ2 and pseudopox virus strain nucleic acid fragments from two or more poxvirus strains selected from the group consisting of TJS; (ii) one or more anticancer nucleic acid sequences; or (iii) a detectable moiety encoding nucleic acid sequence.

In another embodiment is a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, nucleic acid fragments from vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Radle-Elora, and vaccinia virus strain AS; (ii) one or more anticancer nucleic acid sequences; or (iii) a detectable moiety encoding nucleic acid sequence.

In another embodiment is a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises (i) nucleic acid fragments from pox virus strain NZ2 and pseudo vaccinia virus strain TJS; (ii) one or more anticancer nucleic acid sequences; or (iii) a detectable moiety encoding nucleic acid sequence.

in another aspect A chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 3, wherein the nucleic acid sequence comprises (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, nucleic acid fragments from vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Panoma, and vaccinia virus strain AS; (ii) one or more anticancer nucleic acid sequences; or (iii) a detectable moiety encoding nucleic acid sequence.

In one embodiment is a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, wherein the nucleic acid sequence is (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia virus strain Radle-Pantyno, vaccinia virus strain AS, sheeppox virus strain NZ2 and pseudo nucleic acid fragments from two or more poxvirus strains selected from the group consisting of vaccinia virus strain TJS; (ii) one or more anticancer nucleic acid sequences; (iii) one or more nucleic acid binding sequences; or (iv) a detectable moiety encoding nucleic acid sequence.

In another embodiment is a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises (i) vaccinia virus strain Brighton, raccoonpox virus strain Herman, rabbitpox virus strain Utrecht, nucleic acid fragments from vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Elora, and vaccinia virus strain AS; (ii) one or more anticancer nucleic acid sequences; (iii) one or more nucleic acid binding sequences; or (iv) a nucleic acid sequence encoding a detectable moiety.

In another embodiment is a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises (i) nucleic acid fragments from pox virus strain NZ2 and pseudo vaccinia virus strain TJS; (ii) one or more anticancer nucleic acid sequences; (iii) one or more nucleic acid binding sequences; or (iv) a detectable moiety encoding nucleic acid sequence.

In another embodiment is a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 3, wherein the nucleic acid sequence comprises (i) vaccinia virus strain Brighton, raccoonpox virus strain Herman, rabbitpox virus strain Utrecht, nucleic acid fragments from vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Elora, and vaccinia virus strain AS; (ii) one or more anticancer nucleic acid sequences; (iii) one or more nucleic acid binding sequences; or (iv) a nucleic acid sequence encoding a detectable moiety.

Figure 1. Novel chimeric orthopoxvirus isolates #33 (SEQ ID NO: 1) and #17 (SEQ ID NO: 3) have excellent cancer cell killing ability compared to the parent individual wild-type virus strains and control viruses, GLV-1h68 and OncoVEX GFP. indicates
Figure 2. Novel chimeric parapoxvirus isolate #189 (SEQ ID NO: 2) shows excellent cancer cell killing ability compared to the parent individual wild-type virus strain and control viruses GLV-1h68 and OncoVEX GFP.
Figure 3. Novel chimeric orthopoxvirus isolates #17 (SEQ ID NO: 3) and #33 (SEQ ID NO: 1) exhibit strong cancer cell killing ability in pancreatic cancer cell lines compared to their parental virus strains and control viruses, GLV-1h68 and OncoVEX GFP. indicate
Figure 4. Novel chimeric parapoxvirus isolate #189 (SEQ ID NO: 2) shows potent cancer cell killing ability in pancreatic cancer cell lines compared to its parent virus strain and control viruses GLV-1h68 and OncoVEX GFP.
Figures 5a-5c. Novel chimeric virus isolates #33 (SEQ ID NO: 1) and #189 (SEQ ID NO: 2) exhibit excellent apoptotic activity in gastric cancer cell lines. Cancer cells were infected with each virus at MOIs of 0.01, 0.1 and 1.0. Cell viability was plotted against MOI in the above cell lines MKN-45 (FIG. 5A), OCUM-2M (FIG. 5B) and KATO-3 (FIG. 5C) 96 hours after infection.
Figures 6a-6d. The cytotoxic effect of HOV-189 (SEQ ID NO: 2) in vitro is both time and dose dependent in triple negative breast cancer cell lines (FIG. 6A). Hs578T. LD50, MOI 0.396 (SD 0.113), (FIG. 6B) BT549. LD50, MOI 1.636 (SD 0.539), (Fig. 6c) MDA-MB-468. LD50, MOI 0.185 (SD 0.071), (FIG. 6D) MDA-MB-231. LD50, MOI 1.712 (SD 1.263). LD50 (at 96 hours), median lethal dose; MOI , multiplicity of infection; SD , standard deviation.
Figure 7. Replication of HOV-189 (SEQ ID NO: 2) in triple negative breast cancer cell lines. Efficient viral replication occurred in BT549, Hs578T and MDA-MB-231 cell lines at low multiplicity of infection (MOI 0.01) in vitro. HOV-189 replication in MDA-MB-468 was slow at MOI 0.01. At MOI 10, HOV-189 replication in MDA-MB-468 was almost 2 logs lower than in the other three cell lines.
8 . Intratumoral injection of HOV-189 (SEQ ID NO: 2) in MDA-MB-468 xenografts effectively reduces relative tumor size at doses as low as 10 ³ PFU per tumor compared to controls. Tumors with an initial tumor volume of about 100 to 150 mm ³ were injected with PBS (control), 10 ³ PFU per tumor, 10 ⁴ PFU per tumor or 10 ⁵ PFU per tumor. Tumor size was measured approximately every 3 days and the therapeutic effect lasted 6 weeks after injection.
Figure 9. No significant decrease in relative body weight was observed in nude mice treated with intratumoral HOV-189 (SEQ ID NO: 2) injection compared to PBS injection controls. Body weight was measured approximately every 3 days.
10a-10c. MDA-MB-468 tumors are infected in vivo with HOV-189 (SEQ ID NO: 2). Immunofluorescence detection of polyclonal antibodies against sheeppox virus demonstrates viral infection of MDA-MB-468 xenograft tumor tissue harvested 1 week after intratumoral HOV-189 injection. (FIG. 10A) Control tumor, 10X, (FIG. 10B) 10 ⁵ U PFU-treated group tumor, 10X, (FIG. 10C), 10 ⁵ PFU-treated group tumor, 60X. (ORF and DAPI counterstaining).
Figure 11. Intratumoral injection of HOV-189 (SEQ ID NO: 2) shows tumor suppressive effects in distant uninjected tumors. The second breast tumor generated in the MDA-MB-468 xenograft received a single intratumoral injection of 10 ⁵ PFU of HOV-189, but not the fourth breast tumor. Control tumors were injected with PBS. Tumor size was measured approximately every 3 days.
12a-12l. PANC-1, MiaPaCa-2, BxPC-3, SU.86.86, Capan-1 and AsPC-PC were plated for 24 hours at 3x10 ³ cancer cells per well in 100 μl RPMI, 5% FBS, 1% antibiotic-antimycotic solution. -1 A cytotoxicity assay was performed on cancer cell lines. Then, 20 μl of the indicated viruses were added at multiplicities of infection (MOI) 1, 0.1 and 0.01. Daily cell viability assays were performed by adding 20 μl of CellTiter 96 Aqueous One Solution Cell Proliferation Assay to all wells and taking colorimetric readings after 1 hour incubation. Experimental results were normalized to medium alone and MOI 0 control. This experiment was repeated in triplicate. PANC-1 (Fig. 12a), MiaPaCa-2 (Fig. 12c), BxPC-3 (Fig. 12e), SU.86.86 (Fig. 12g), Capan-1 (Fig. 12i) treated with #33 at MOI of 1, 0.1 or 0.01. ), and AsPC-1 (FIG. 12K), a graph showing cell viability over time is presented. In addition, PANC-1 (FIG. 12B), MiaPaCa-2 (FIG. 12D), BxPC-3 (FIG. 12F), SU.86.86 (FIG. 12H), Capan-1 (FIG. 12J), and AsPC-1 (FIG. 12J) treated with the indicated viruses. 1 (FIG. 12L) shows a bar graph comparing cell viability at 120 hours for cancer cells. Statistical analysis was performed comparing #33 to the other experimental groups specified using One-Way ANOVA at each time point. For SU.86.86 (FIG. 12H), statistical analysis was performed using an unpaired t-test at each MOI.
13a-13l. Cells at 5x10 ⁵ cells per well were plated in triplicate for 24 hours in 2mL RPMI, 10% FBS, 1% antibiotic-antimycotic solution, and PANC-1, MiaPaCa-2, BxPC-3, SU.86.86, Capan-1 and Viral replication curves were performed in the AsPC-1 cancer cell line. The medium was then aspirated and #33, OncoVEX GFP, GLV-1h68, or #189 was cultured at a multiplicity of infection (MOI) of 0.01 in 500 μl of RPMI, 2.5% FBS, 1% antibiotic-antimycotic solution every 20 minutes with shaking at 1 added over time. After 1 hour, the medium was aspirated and 1.5 mL of RPMI, 2.5% FBS, 1% antibiotic-antimycotic solution was added. Cells and supernatant were collected at 24, 48 and 72 hours, and serial dilutions were performed in duplicate after three freeze-thaw cycles. This experiment was repeated in duplicate. PANC-1 (FIG. 13A), MiaPaCa-2 (FIG. 13C), BxPC-3 (FIG. 13E), SU.86.86 (FIG. 13G), Capan-1 (FIG. 13I), and AsPC-1 (FIG. 13I) treated with the indicated viruses. 13K ) A graph showing PFU/10 ⁶ cells over time for cancer cells is presented. In addition, PANC-1 (FIG. 13b), MiaPaCa-2 (FIG. 13d), BxPC-3 (FIG. 13f), SU.86.86 (FIG. 13h), Capan-1 (FIG. 13j) and AsPC-1 (FIG. 13l) Bar graphs comparing PFU/10 ⁶ cells at each time point for each virus in treated cancer cells are presented. Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point.
14a-14c. Eighteen athymic Nude- Foxn1 ^nu female nude mice (Envigo, Indianapolis, IN) were injected with 2x10 ⁶ cells per flank tumor. MiaPaCa-2 was implanted. When the tumor size reached 400 mm ³ , 50 μl of PBS (3 mice), #33 (5 mice), #33-(SE)hNIS or #33-(SE)hNIS-E9LmiR100t (5 mice) was administered to the left tumor. were injected at approximately 1x10 ⁵ PFU per dose. Net weight change (FIG. 14A) and change rate (FIG. 14B) of injected tumors and change rate of non-injected tumors (FIG. 14C) were recorded twice weekly for 43 days.
15a-15c. Twenty-six athymic Nude- Foxn1 ^nu female nude mice (Envigo, Indianapolis, IN) were implanted with 1.25x10 ⁶ PANC-1 per flank tumor. When the tumor size reached approximately 250 mm ³ , 50 μl of PBS (4 mice), #33 (6 mice), #33-(SE)hNIS (6 mice), #33-(SE)hNIS-E9LmiR100t ( 5) or #33-(H5)Fluc2 at approximately 1x10 ³ PFU per dose. Net weight change (FIG. 15A) and change rate (FIG. 15B) of injected tumors and change rate of non-injected tumors (FIG. 15C) were recorded twice weekly for 43 days.
16. Twice weekly, 1 PBS control mouse and 3 #33-(H5)Fluc2 injected mice were intraperitoneally injected with 4.28 mg of luciferin in 150 μl of PBS. After 7 minutes, luciferase images were obtained at standard exposures. Relative units at each time point were recorded and analyzed relative to PBS control mice as background.
17a-17d. Cytotoxicity assays were performed on HT-29 and HCT-116 cancer cell lines by plating 3×10 ³ cells per well in 100 μl McCoy's 5A medium, 5% FBS, 1% antibiotic-antimycotic solution for 24 hours. Then, 20 μl of each of the viruses, #33, #33-(SE)hNIS, #33(H5)Emerald, OncoVEX ^GFP , GLV-1h68, or #189 was administered at multiple infectivity levels (MOIs) of 1, 0.1, and 0.01. was added as Daily cell viability assays were performed by adding 20 μl of CellTiter 96 Aquas One Solution Cell Proliferation Assay to all wells and taking colorimetric readings after 1 hour incubation. Experimental results were normalized to medium alone and MOI 0 control. This experiment was repeated in triplicate. Graphs showing cell viability over time are presented for HT-29 (FIG. 17A) and HCT-116 (FIG. 17C) treated with #33 at MOIs of 1, 0.1, or 0.01. Also presented is a bar graph comparing cell viability at 120 hours for HT-29 (FIG. 17B) and HCT-116 (FIG. 17D) cancer cells treated with the indicated viruses. Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point.
18a-18f. Cytotoxicity assays were performed on SW620, SW480, and COLO 320DM cancer cell lines by plating 3×10 ³ cells per well in 100 μl RPMI, 5% FBS, 1% antibiotic-antimycotic solution for 24 hours. Then, 20 μl of each of the viruses, #33, #33-(SE)hNIS, #33(H5)Emerald, OncoVEX ^GFP , GLV-1h68, or #189 was administered at multiple infectivity levels (MOIs) of 1, 0.1, and 0.01. was added as Daily cell viability assays were performed by adding 20 μl of CellTiter 96 Aquas One Solution Cell Proliferation Assay to all wells and taking colorimetric readings after 1 hour incubation. Experimental results were normalized to medium alone and MOI 0 control. This experiment was repeated in triplicate. Graphs showing cell viability over time are presented for SW620 (FIG. 18A), SW480 (FIG. 18C), and COLO 320DM (FIG. 18E) treated with #33 at an MOI of 1, 0.1, or 0.01. Also presented is a bar graph comparing cell viability at 120 hours for SW620 (FIG. 18B), SW480 (FIG. 18D), and COLO 320DM (FIG. 18F) cancer cells treated with the indicated viruses. Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point. "NS" above the comparison bar means "not significant".
19a-19b. Cytotoxicity assay was performed on the LoVo cancer cell line by plating 3×10 ³ cells per well in 100 μl F-12K medium, 5% FBS, 1% antibiotic-antimycotic solution for 24 hours. Then, 20 μl of each of the viruses, #33, #33-(SE)hNIS, #33(H5)Emerald, OncoVEX ^GFP , GLV-1h68, or #189 was administered at multiple infectivity levels (MOIs) of 1, 0.1, and 0.01. was added as Daily cell viability assays were performed by adding 20 μl of CellTiter 96 Aquas One Solution Cell Proliferation Assay to all wells and taking colorimetric readings after 1 hour incubation. Experimental results were normalized to medium alone and MOI 0 control. This experiment was repeated in triplicate. [Fig. 19a] shows the cell viability over time for LoVo cancer cells treated with #33 at an MOI of 1, 0.1, or 0.01. 19B also shows a bar graph comparing cell viability at 120 hours for LoVo cancer cells treated with the indicated viruses. Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point. "NS" above the comparison bar means "not significant".
20a-20d. Viral replication curves were performed in HT-29 and HCT-116 cancer cell lines by plating cells at 5x10 ⁵ cells per well in triplicate for 24 hours in 2mL McCoy's 5A medium, 10% FBS, 1% antibiotic-antimycotic solution. Then, the medium was aspirated, and #33, #33-(SE)hNIS, #33-(H5)Emerald, OncoVEX ^GFP , GLV-1h68, or #189 was added to 500 μl McCoy 5A medium, 2.5% FBS, 1% A multiplicity of infection degree (MOI) of 0.01 in an antibiotic-antimycotic solution was added for 1 hour with shaking every 20 minutes. At 1 hour, the medium was aspirated and 1.5 mL of McCoy's 5A medium, 2.5% FBS, 1% antibiotic-antimycotic solution was added. At 24, 48, and 72 hours, cells and supernatant were collected, and after three freeze-thaw cycles, serial dilutions were performed in duplicate. This experiment was repeated in duplicate. A graph showing PFU/10 ⁶ cells over time is shown for HT-29 (FIG. 20A) and HCT-116 (FIG. 20C). Also presented are histograms comparing PFU/10 ⁶ cells at each time point for each virus in treated cancer cells from HT-29 (FIG. 20B) and HCT-116 (FIG. 20D). Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point.
21a-21d. Viral replication in SW620 (FIGS. 21A-21B) and SW480 (FIGS. 21C-21D) cancer cell lines by plating cells at 5x10 ⁵ cells per well in triplicate for 24 hours in 2mL RPMI, 10% FBS, 1% antibiotic-antimycotic solution. curve was performed. The medium was then aspirated and #33, #33-(SE)hNIS, #33-(H5)Emerald, OncoVEX ^GFP , GLV-1h68, or #189 was added to 500 μl of RPMI 2.5% FBS, 1% antibiotic- In antifungal solution, a multiplicity of infection degree (MOI) of 0.01 was added for 1 hour with shaking every 20 minutes. At 1 hour, the medium was aspirated and 1.5 mL of RPMI 2.5% FBS, 1% antibiotic-antimycotic solution was added. At 24, 48, and 72 hours, cells and supernatant were collected, and after three freeze-thaw cycles, serial dilutions were performed in duplicate. This experiment was repeated in duplicate. A graph showing PFU/10 ⁶ cells over time is presented for SW620 (FIG. 21A) and SW480 (FIG. 21C). Also presented are histograms comparing PFU/10 ⁶ cells at each time point for each virus in treated cancer cells of SW620 (FIG. 21B) and SW480 (FIG. 21D). Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point.
Figure 22. Immunohistochemical analysis of HCT-116 cancer cells infected with virus #33 or #33-(SE)hNIS. Images taken 24 hours after infection with an MOI of 0.01.
Figure 23. Immunohistochemical analysis of HT-29 cancer cells infected with virus #33 or #33-(SE)hNIS. Images taken 24 hours after infection with an MOI of 0.01.
24. Fourteen athymic Nude- Foxn1 ^nu female nude mice (Envigo, Indianapolis, IN) were implanted with 5×10 ⁶ cells of HT-29 per flank tumor. When tumor size reaches approximately 200 mm ³ , both tumors are injected with approximately 1x10 ⁵ PFU per dose of 50 μl of PBS (4 mice), #33 (5 mice), or #33-(H5)Fluc2 (5 mice). did Net weight change and rate of change of tumors were recorded twice weekly for 42 days. [Figure 24] shows the HT-29 tumor change rate over time. Significant differences were found in tumor volume change rates when the PBS control group was compared to #33 (three mice) and #33-(H5)Fluc2 (p = 0.02 and p = 0.03, respectively).
25. Twice weekly, 1 PBS control mouse and 3 #33-(H5)Fluc2 injected mice were intraperitoneally injected with 4.28 mg of luciferin in 150 μl of PBS. After 7 minutes, luciferase images were obtained at standard exposures. Relative units at each time point were recorded and analyzed relative to PBS control mice as background.
26. Nineteen athymic Nude- Foxn1 ^nu female nude mice (Envigo, Indianapolis, IN) were implanted with 5x10 ⁶ HCT-116 per flank tumor. When the tumor size reached approximately 200 mm ³ , 50 μl of PBS (2 mice), #33 (3 mice), #33-(SE)hNIS, or #33-(H5)Fluc2 was administered to both tumors approximately 1x10 per dose. Injected with ⁵ PFU. Net weight change and rate of change of tumors were recorded twice weekly for 42 days. [Figure 25] shows the rate of change in HCT-116 tumors over time. Significant change in tumor volume when PBS control was compared to #33 (three mice), #33-(SE)hNIS and #33-(H5)Fluc2 (p = p = 0.0002, p = 0.0001 and p = 0.0002, respectively) A difference appeared.
27. Twice weekly, 1 PBS control mouse and 3 #33-(H5)Fluc2 injected mice were intraperitoneally injected with 4.28 mg of luciferin in 150 μl of PBS. After 7 minutes, luciferase images were obtained at standard exposures. Relative units at each time point were recorded and analyzed relative to PBS control mice as background.
28a-28c. Oncolytic virus-mediated cytotoxicity in lung cancer and lung fibroblasts 72 h after infection. 5000 cells of A549, H2199 or HF1 fibroblasts were plated in each well of a 96-well plate. The next day, cells were infected with different viruses (#33, #33-(H5)Emerald, #189, GLV-1h68, OncoVEX ^GFP ) at the indicated multiplicities of infection (MOI: 0, 0.001, 0.01, 0.1, 1 MOI). or mock infection. Cell viability was determined 72 hours after infection using CellTiter 96 Aquas One Solution (Promega; Cat # G3581). The viability of infected A549 cells (FIG. 28A), H2199 cells (FIG. 28B) or HF1 fibroblasts (FIG. 28C) was calculated relative to the viability of mock-infected cells.
29. GFP imaging for several days in an A549 xenograft model following a single intratumoral injection of 1000 PFU of virus (#33-(H5)Emerald, GLV-1h68 or OncoVEX ^GFP ) as indicated in the tumor on the right.
Figure 30. Body weight of mice over several days in the A549 xenograft model. Three weeks after tumor cell A549 injection, mice were grouped into different treatment groups (n = 4 or 5) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group and 10 ³ PFU of the specified amount was injected into the right tumor of each mouse. Intratumoral injection of virus (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM , #189, PBS control) or intraperitoneal (ip) injection of #33-(H5)Emerald did The mice were weighed twice a week and the percentage change in body weight was shown. Each line represents the body weight of an individual mouse.
31a-31b. Tumor regression in the A549 xenograft model. Three weeks after tumor cell A549 injection, mice were grouped into different treatment groups (n = 4 or 5) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group and 10 ³ PFU of the specified amount was injected into the right tumor of each mouse. Intratumoral injection of virus (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM , #189, PBS control) or intraperitoneal (ip) injection of #33-(H5)Emerald did Twice weekly, injected (FIG. 31A) and non-injected (FIG. 31B) tumor volumes were measured using a digital caliper. Each line represents the tumor volume of an individual mouse.
Figure 32. Volume of virus injected tumors in A549 xenograft model. Three weeks after tumor cell A549 injection, mice were divided into different treatment groups (n = 4 or 5) to obtain similar average tumor volumes (~200 mm ³ ) in each group, and 10 ³ PFU of 10 3 PFU was injected into the right tumor of each mouse. Intratumoral injection with the indicated viruses (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM , #189, PBS control) or #33-(H5)Emerald intraperitoneally (ip) Injected. Tumor volume was measured using a digital caliper twice weekly. Each line represents the average volume of tumors injected with standard deviation in an individual treatment group. Statistical Analysis: One-way ANOVA at Day 24 (* = p <0.05).
Figure 33. Volume of uninjected tumors in the A549 xenograft model. Three weeks after tumor cell A549 injection, mice were grouped into different treatment groups (n = 4 or 5) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group and only the right tumor of each mouse received 10 ³ PFU of the specified Intratumoral injection of virus (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM , #189, PBS control) or intraperitoneal (ip) injection of #33-(H5)Emerald did Twice weekly, uninjected tumor volume was measured using a digital caliper. Each line represents the average volume of uninjected tumors with standard deviation in an individual treatment group. Statistical Analysis: One-way ANOVA at Day 24 (* = p <0.05).
34a-34b. Fold change in tumor volume. Three weeks after tumor cell A549 injection, mice were grouped into different treatment groups (n = 4 or 5) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group and 10 ³ PFU of the specified amount was injected into the right tumor of each mouse. Intratumoral injection of virus (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM , #189, PBS control) or intraperitoneal (ip) injection of #33-(H5)Emerald did Tumor volume was measured using a digital caliper twice weekly. Fold change in tumor volume for injected (FIG. 34A) and non-injected (FIG. 34B) tumors was calculated by normalizing the tumor volume at different time points with the tumor volume at the time of virus injection (i.e., day 0). In Figures 34A-34B, each line represents the average tumor volume with standard deviation for an individual treatment group. Statistical Analysis: One-way ANOVA at Day 24 (* = p <0.05).
35a-35b. Biodistribution of virus in injected and non-injected tumors (A549 model). Three weeks after tumor cell A549 injection, mice were grouped into different treatment groups (n = 3) to obtain similar average tumor volumes (~200 mm ³ ) in each group and 10 ³ PFU of the specified virus ( #33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^™ ) were injected intratumorally. Six days after virus injection, tumors and normal organs were harvested. The harvested tissue was weighed, minced into small pieces and homogenized in 1 ml PBS using a Bullet Blender Gold homogenizer. The homogenates were subjected to 3 freeze-thaw cycles followed by 1 minute sonication. The homogenate was spun down at 1000 rpm for 3 minutes and the supernatant was collected. Supernatants were serially diluted and viral titers were determined using a standard plaque assay. [FIG. 35A] shows PFU per gram of tumor for each virus in injected tumors, and [FIG. 35B] shows PFU per gram of tumor for each virus in uninjected tumors.
Figure 36. Titer of virus in ovaries of mice (A549 model). Three weeks after tumor cell A549 injection, mice were grouped into different treatment groups (n = 3) to obtain similar average tumor volumes (~200 mm ³ ) in each group and 10 ³ PFU of the specified virus ( #33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^™ ) were injected intratumorally. Six days after virus injection, tumors and normal organs were harvested. The harvested tissue was weighed, minced into small pieces and homogenized in 1 ml PBS using a Bullet Blender Gold homogenizer. The homogenates were subjected to 3 freeze-thaw cycles followed by 1 minute sonication. The homogenate was spun down at 1000 rpm for 3 minutes and the supernatant was collected. Supernatants were serially diluted and viral titers were determined using a standard plaque assay. [Fig. 36] shows PFU per gram of tissue (ovary) for each virus. Not detected (ND).
37. Virus titer in blood 20 days after virus injection. Three weeks after tumor cell A549 injection, mice were grouped into different treatment groups (n = 3) to obtain similar average tumor volumes (~200 mm ³ ) in each group and 10 ³ PFU of the specified virus ( #33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^™ ) were injected intratumorally. Blood was collected from mice (n = 3) via facial vein puncture. After three freeze-thaw cycles, blood was serially diluted and viral titers were determined using a standard plaque assay. Figure 37 shows the PFU per ml of blood for each virus injected. Not detected (ND).
38. Chimeric virus #33 is more potent than the parental virus in killing lung cancer cells (A549). Cytotoxicity assay: 5000 cells were plated in each well of a 96-well plate. The following day, cells were infected or mock-infected at the multiplicity of infection (MOI) specified for the chimeric virus #33 or the parental virus. Cell viability was determined using CellTiter 96 Aquas One Solution (Promega; Cat # G3581) 72 hours after infection. The viability of infected cells was calculated relative to the viability of mock-infected cells.
39. Weight change after treatment. A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 4 or 5) to obtain similar mean tumor volumes (˜200 mm ³ ) in each group. After sorting, only the right tumor of each mouse was injected intratumorally with 10 ³ PFU of the indicated virus. Mice were weighed twice weekly and the percent change in body weight was plotted. Each line represents the body weight of an individual mouse.
40. Tumor regression. A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 4 or 5) to obtain similar mean tumor volumes (˜200 mm ³ ) in each group. After sorting, only the right tumor of each mouse was injected intratumorally with 10 ³ PFU of the indicated virus. Tumor volumes (both injected and uninjected) were measured using a digital caliper twice weekly (volume = {(length) ² x (width)/2}). Each line represents the tumor volume of an individual mouse.
Figure 41. Viral titers in injected and non-injected tumors 7 days after infection. A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 3) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group. After sorting, only the right tumor of each mouse was injected intratumorally with 10 ³ PFU of the indicated virus. Six days after virus injection, tumors and normal organs were harvested. The harvested tissue was weighed, minced into small pieces and homogenized in 1 ml PBS using a Bullet Blender Gold homogenizer. The homogenates were subjected to 3 freeze-thaw cycles followed by 1 minute sonication. The homogenate was spun down at 1000 rpm for 3 minutes and the supernatant was collected. Supernatants were serially diluted and viral titers were determined using a standard plaque assay.
42. Biodistribution of viruses. A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 3) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group. After sorting, only the right tumor of each mouse was injected intratumorally with 10 ³ PFU of the indicated virus. Six days after virus injection, tumors and normal organs were harvested. The harvested tissue was weighed, minced into small pieces and homogenized in 1 ml PBS using a Bullet Blender Gold homogenizer. The homogenates were subjected to 3 freeze-thaw cycles followed by 1 minute sonication. The homogenate was spun down at 1000 rpm for 3 minutes and the supernatant was collected. Supernatants were serially diluted and viral titers were determined using a standard plaque assay.
43. Viral titers in the blood of injected mice. Blood was collected from the facial veins of A549 tumor-bearing mice at different time points after intratumoral injection of 1000 pfu of the indicated virus. Virus in blood samples was titered using standard plaque assay techniques. No virus was detected in urine until day 10 after injection.
44. Survival rate of mice after virus injection. A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 3) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group. After sorting, only the right tumor of each mouse was injected intratumorally with 10 ³ PFU of the indicated virus. Tumor volumes were measured twice weekly using digital calipers and mice were euthanized when either tumor exceeded the tumor burden (3000 mm ³ ) or when the mice became ill (weight >20% loss) due to viral treatment .
45a-45c. Comparison of the cytotoxic potential of chimera #33 and the parental poxvirus in A549. Fig. 45a. For all viruses, the MOI (LD50) of the virus required to kill 50% of A549 cells was calculated and compared. Fig. 45b. Cells were infected with #33 or parental virus at an MOI of 0.03 pfu, and the fold increase in viral titer relative to the input virus was determined 24 hours after infection and compared between viruses. Fig. 45c. A549 cells were infected with the virus as in [FIG. 45B], and supernatants obtained from infected wells were collected at 12 and 18 hours after infection. Viral titers in supernatants were determined by plaque assay and compared between viruses.
46a-46b. A549 cells were infected at different MOIs with #33 or #33-(H5)Emerald in which the J2R (TK) gene was replaced with an Emerald (green) expression cassette. Fig. 46a. 5000 cells were plated in each well of a 96-well plate. The next day, cells were infected at different MOIs with chimeric virus #33-(H5)Emerald in which the #33 or J2R (TK) gene was replaced with an emerald (green) expression cassette. Cell viability was determined 72 hours after infection using CellTiter 96 Aquas One Solution (Promega; Cat # G3581). The viability of infected cells was calculated relative to the viability of mock-infected cells. Fig. 46b. A549 cells were infected with #33 or #33-(H5) at an MOI of 0.03 pfu and the fold increase in viral titer relative to the input virus was determined at the indicated time points.
47a-47b. Fig. 47a. Imaging: A549 human lung cancer cells were cultured, trypsinized, washed with PBS and resuspended in 1:1 PBS and Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 5) to obtain similar mean tumor volumes (~ 200 mm ³ ) in each group. After sorting, only the right tumor of each mouse was injected intratumorally with 10 ³ plaque forming units (PFU) of #33-(H5)Emerald or PBS. Mice were imaged twice weekly for green fluorescence (excitation: 465 and emission: 530 nm) using small animal imaging equipment (LagoX imaging system) and images were processed with AMIview image processing software. Fig. 47b. Mean fluorescence intensity (MFI) of Emerald was calculated for each tumor at different time points using AMIview image processing software. Mean MFI for injected and non-injected tumors (n = 5/group) were compared.
48a-48d. Fig. 48a. A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 7) to obtain similar mean tumor volumes (~ 200 mm ³ ) in each group. After sorting, only the right tumor of each mouse was injected intratumorally with 10 ³ plaque forming units (PFU) of #33-(H5)Emerald or PBS. Mice were weighed twice weekly and the percentage change in body weight was plotted. Each line represents the body weight of an individual mouse. Fig. 48b. Tumor volume was measured using a digital caliper twice weekly (volume = {(length) ² x width/2}). Each line represents the mean volume of tumors injected with SD in an individual treatment group. Statistics: Unpaired T-test; ****=p<0.0001. ** 33-GFP indicates animals treated with #33-(H5)Emerald. Fig. 48c. Tumor volumes for individual mice in each treatment group were plotted. Fig. 48d. When one of the tumors on both sides exceeded the tumor burden (3000 mm ³ ), they were euthanized, and the survival curves of the virus-treated group were compared with those of the PBS-treated group. Statistics: Log-rank (Mantel Cox) test; ****=p<0.0001.
49a-49c. Fig. 49a. A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 4 or 5) to obtain similar mean tumor volumes (˜200 mm ³ ) in each group. After sorting, only the right tumor of each mouse was injected intratumorally with 10 ³ PFU of the indicated virus. On days 7 and 56 after virus injection, 3 mice from the virus-treated group were euthanized and their organs and tumors were harvested. Viral titers of harvested organs were determined by plaque assay and tumors and organs were compared. Statistics: one-way ANOVA; *** = p < 0.0001. ND = not detected. Fig. 49b. Tumor sections (7 days after virus injection) were stained for vaccinia virus. Dark staining indicates areas of viral infection in tumor sections. Each section is from a separate mouse. Fig. 49d. Tumor sections obtained 7 days after virus injection were stained for apoptotic cells using In Situ Cell death detection Fluorescein (Roche). For the 'positive control', tumor sections were treated with recombinant Dnase I (300 U/ml) for 10 minutes at room temperature. Gray signals represent apoptotic cells.
Figure 50. In vitro cytotoxicity of OVCAR8 cells (72 hours post infection). 5000 OVCAR8 (human ovarian cancer) cells were plated in each well of a 96-well plate. The next day, cells were infected with chimeric virus #33 or #33 virus with TK deleted (#33/TK-) or with miR100 and Let-7c target sequences inserted into the essential viral genes E9L or D4R . Infections were performed at the specified multiplicity of infection (MOI). Cell viability was determined 72 hours after infection using CellTiter 96 Aquas One Solution (Promega; Cat # G3581). The viability of infected cells was calculated relative to the viability of mock-infected cells.
Figure 51. Viral growth kinetics of OVCAR8 cells. OVCAR8 cells were infected with the indicated viruses at an MOI of 0.03 pfu in 6-well plates. Cell lysates were collected from infected wells at 24, 48 and 72 hours post infection. Viral titers in cell lysates were determined by plaque assay and the fold increase in viral titer versus input virus was plotted.
52. Rate of change in body weight of mice. Human ovarian cancer cells, OVCAR8, were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 8 for PBS and n = 5 for all other groups) to obtain similar mean tumor volumes (˜200 mm ³ ) in each group. After sorting, only the right tumor of each mouse was injected intratumorally with 10 ⁵ PFU of the indicated virus. Mice were weighed twice weekly and the percent change in body weight was plotted. Each line represents the body weight of an individual mouse.
53. Tumor volume. Human ovarian cancer cells, OVCAR8, were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 8 for PBS and n = 5 for all other groups) to obtain similar mean tumor volumes (˜200 mm ³ ) in each group. After sorting, only the right tumor of each mouse was injected intratumorally with 10 ⁵ PFU of the indicated virus. Tumor volume was measured using a digital caliper twice weekly (volume = {(length) ² x width/2}). The volume of virus-injected and non-injected tumors was plotted for individual mice in each treatment group.
54a-54b. Mean tumor volume of injected and non-injected tumors. Human ovarian cancer cells, OVCAR8, were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 8 for PBS and n = 5 for all other groups) to obtain similar mean tumor volumes (˜200 mm ³ ) in each group. After sorting, only the right tumor of each mouse was injected intratumorally with 10 ⁵ PFU of the indicated virus. Tumor volume was measured using a digital caliper twice weekly (volume = {(length) ² x width/2}). Mean tumor volume was plotted with SD for each treatment group. 54A and 54B show mean tumor volume with SD for injected and non-injected tumors, respectively.
55. Viral titers in organs 7 days after infection. Human ovarian cancer cells, OVCAR8, were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 3) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group. After sorting, only the right tumor of each mouse was injected intratumorally with 10 ⁵ PFU of the indicated virus. Mice were euthanized on day 7 after virus injection and tumors and organs were harvested. Viral titers of harvested organs were determined by plaque assay and compared between tumors and organs. Note: Virus was not detected in normal organs (lungs, liver, ovaries, kidneys, spleen and brain) and in uninjected tumors.
56. miR100 in OVCAR8 tumors and mouse organs. Athymic nude mice (n = 3) bearing OVCAR8 xenografts were euthanized and tumors and organs harvested. The harvested tissue was homogenized and total RNA was isolated using the miRNeasy mini kit (Qiagen). Real-time PCR was performed to determine the level of miR-100 in the lysate.
57. Let-7c in OVCAR8 tumors and mouse organs. Athymic nude mice (n = 3) bearing OVCAR8 xenografts were euthanized and tumors and organs harvested. The harvested tissue was homogenized and total RNA was isolated using the miRN Easy Mini Kit (Qiagen). Real-time PCR was performed to determine the level of Let-7c in the lysate.

Described herein are chimeric poxvirus compositions that combine advantageous features from different viral species to create novel hybrid chimeric poxviruses that are superior to individual wild-type viruses. Applicants have generated chimeric poxviruses from different genera. Chimeric orthopoxvirus and parapoxvirus isolates showed superior killing capacity compared to their parental individual wild-type viruses in the NCI panel of 60 cancer cell lines. In addition, taking advantage of the fact that members of the different genera of the poxviride family differ antigenically, it is possible to combine the potent chimeric orthopoxvirus and the potent chimeric parapoxvirus generated in this study in the same treatment regimen to achieve maximal treatment efficacy can be achieved.

I. Definition

Although various embodiments and aspects of the present invention have been shown and described herein, it will be apparent to those skilled in the art that these embodiments and aspects are provided by way of example only. Various modifications, alterations and substitutions will occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be used in practicing the invention.

Section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents or portions of documents cited in this application, including without limitation patents, patent applications, articles, books, manuals and monographs, are hereby expressly incorporated by reference in their entirety for all purposes.

Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. See, eg, Singleton et al., DICTIONARY OF MICROBIOLOGY AND MOLECULAR BIOLOGY 2nd ed., J. Wiley & Sons (New York, NY 1994); Sambrook et al., MOLECULAR CLONING, A LABORATORY MANUAL, Cold Springs Harbor Press (Cold Springs Harbor, NY 1989). Any methods, devices, and materials similar or equivalent to those described herein can be used in the practice of the present invention. The following definitions are provided to aid in the understanding of certain terms used frequently herein and are not intended to limit the scope of the present invention.

The term "isolated" or "isolated" when applied to a nucleic acid, virus or protein means that the nucleic acid, virus or protein is essentially free of other cellular components associated with it in its natural state. It may be in a homogeneous state, for example, and may be in anhydrous or aqueous solution. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. Proteins, which are the major species present in the formulation, are substantially purified.

As used herein, "nucleic acid" or "oligonucleotide" or "polynucleotide" or grammatical equivalents means two or more nucleotides covalently linked together. The term “nucleic acid” refers to deoxyribonucleotides or ribonucleotides and polymers thereof, or their complements, in single or double-stranded form. The term “polynucleotide” refers to a linear series of nucleotides. The term "nucleotide" typically refers to a single unit of polynucleotide, i.e., a monomer. Nucleotides may be ribonucleotides, deoxyribonucleotides or modified forms thereof. Examples of polynucleotides contemplated herein include single and double stranded DNA, single and double stranded RNA (including siRNA), and hybrid molecules having mixtures of single and double stranded DNA and RNA. The term also includes nucleic acids containing known nucleotide analogs or modified backbone residues or linkages, which are synthetic, naturally occurring and non-naturally occurring, have binding properties similar to the reference nucleic acid, and are metabolized in a manner similar to the reference nucleotide. do. Examples of such analogs include, without limitation, phosphorothioates, phosphoramidates, methyl phosphonates, chiral-methyl phosphonates, and 2-O-methyl ribonucleotides.

Nucleic acids may include non-specific sequences. As used herein, the term “non-specific sequence” refers to a nucleic acid sequence that contains a set of residues that are not designed to be complementary or are only partially complementary to any other nucleic acid sequence. By way of example, a non-specific nucleic acid sequence is a sequence of nucleic acid residues that does not function as an inhibitory nucleic acid when contacted with a cell or organism. An “inhibitory nucleic acid” is capable of binding to a target nucleic acid (eg, mRNA that can be translated into a protein) and reducing transcription of the target nucleic acid (eg, mRNA from DNA) or of a target nucleic acid (eg, mRNA that can be translated into a protein). nucleic acids (eg, DNA, RNA, polymers of nucleotide analogues) that can reduce translation of mRNA) or that can alter transcript splicing (eg, single-stranded morpholino oligos).

A "labeled nucleic acid or oligonucleotide" is linked to a label either covalently through a linker or chemical bond, or non-covalently through ionic, van der Waals, electrostatic, or hydrogen bonding, to indicate the presence of a detectable label bound to a nucleic acid. The presence of nucleic acids can be detected by detection. Alternatively, methods using high-affinity interactions can achieve the same results when one of the binding partners of a pair binds to the other, eg biotin, streptavidin. In an embodiment, the phosphorothioate nucleic acid or phosphorothioate polymer backbone comprises a detectable label as disclosed herein and generally known in the art.

The word “complementary” or “complementarity” refers to the ability of a nucleic acid in a polynucleotide to form base pairs with another nucleic acid in a second polynucleotide. For example, sequence A-G-T is complementary to sequence T-C-A. Complementarity can be partial, where only some of the nucleic acids pair base-pairwise, or complete, where all nucleic acids pair base-pairwise.

A nucleic acid is “operably linked” when it is placed into a functional relationship with another nucleic acid sequence. For example, when a polypeptide is expressed as a preprotein that participates in the secretion of the polypeptide, the DNA of the presequence or secretory leader is operably linked to the DNA of the polypeptide. A promoter or enhancer is operably linked to a coding sequence if it affects transcription of the sequence; or the ribosome binding site is operably linked to a coding sequence when positioned to facilitate translation. Generally, “operably linked” means that the DNA sequences being linked are close to each other, and in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Ligation is accomplished by ligation at convenient restriction sites. If no such site exists, synthetic oligonucleotide adapters or linkers are used in accordance with conventional practice.

The term "gene" refers to a segment of DNA involved in protein production. It includes regions preceding and preceding coding regions (leaders and trailers) as well as intervening sequences (introns) between individual coding segments (exons). Leaders, trailers and introns contain regulatory elements necessary for transcription and translation of genes. Also, a "protein gene product" is a protein expressed from a specific gene.

The words "expression" or "expressed" as used herein in reference to a gene refer to the product of transcription and/or translation of that gene. The expression level of a DNA molecule in a cell can be determined based on the amount of the corresponding mRNA present in the cell or the amount of protein encoded by the DNA produced by the cell. Expression levels of non-coding nucleic acid molecules (eg, siRNA) can be detected by standard PCR or Northern blot methods well known in the art. See Sambrook et al ., 1989 Molecular Cloning: A Laboratory Manual , 18.1-18.88.

"siRNA", "small interfering RNA", "small RNA" or "RNAi" as provided herein refers to a nucleic acid that forms a double-stranded RNA, which when expressed in the same cell as the gene or target gene Or it has the ability to reduce or suppress the expression of a target gene. Complementary portions of nucleic acids that hybridize to form a double-stranded molecule typically have substantial or complete identity. In one embodiment, siRNA or RNAi refers to a nucleic acid that has substantial or complete identity with a target gene and forms a double-stranded siRNA. In an embodiment, the siRNA inhibits gene expression by interfering with the complementary cellular mRNA to inhibit expression of the complementary mRNA, thereby inhibiting gene expression. Typically, a nucleic acid is at least about 15 to 50 nucleotides in length (eg, each complementary sequence of a double-stranded siRNA is 15 to 50 nucleotides in length, and a double-stranded siRNA is about 15 to 50 base pairs in length). In other embodiments, the length is 20 to 30 base nucleotides, preferably about 20 to 25 or about 24 to 29 nucleotides in length, e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 nucleotides in length. Non-limiting examples of siRNAs include ribozymes, RNA decoys, short hairpin RNAs (shRNAs), micro RNAs (miRNAs) and small nucleolar RNAs (snoRNAs).

For example, the term "recombinant" when used in reference to a cell, or a nucleic acid, protein, or vector indicates that the cell, nucleic acid, protein, or vector is modified by introduction of a heterologous nucleic acid or protein or modification of a native nucleic acid or protein; indicates that the cell is derived from a cell so modified. Thus, for example, a recombinant cell expresses a gene that is not found in the cell in its native (non-recombinant) form or, if otherwise expressed, a naturally expressed gene that is abnormally expressed or not expressed at all. Transgenic cells and plants are cells and plants that express heterologous genes or coding sequences, typically as a result of recombinant methods.

The term "heterologous" when used in reference to a portion of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in essentially the same relationship to one another. For example, nucleic acids having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g., a promoter from one source and a coding region from another, are typically produced recombinantly. . Similarly, a heterologous protein refers to a protein that contains two or more subsequences that are not found in nature in the same relationship to each other (eg, a fusion protein).

The term “exogenous” refers to molecules or substances (eg, compounds, nucleic acids or proteins) that originate outside of a given cell or organism. For example, an "exogenous promoter" as referred to herein is a promoter that does not originate from the cell or organism in which it is expressed. Conversely, the terms "endogenous" or "endogenous promoter" refer to a molecule or substance native to or derived from a given cell or organism.

The term "isolated" when applied to a nucleic acid or protein indicates that the nucleic acid or protein is essentially free of other cellular components associated with it in its native state. It may be, for example, in a homogeneous state and may be in anhydrous or aqueous solution. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. Proteins, which are the major species present in the formulation, are substantially purified.

The terms “polypeptide,” “peptide” and “protein” are used interchangeably to refer to a polymer of amino acid residues, wherein the polymer may, in embodiments, be conjugated to moieties that do not consist of amino acids. The term applies to naturally occurring amino acid polymers and non-naturally occurring amino acid polymers, as well as amino acid polymers in which one or more amino acid residues are man-made chemical mimics of the corresponding naturally occurring amino acids. "Fusion protein" means a chimeric protein that encodes two or more separate protein sequences recombinantly expressed as a single moiety.

The terms "peptidyl" and "peptidyl moiety" refer to a monovalent peptide.

The term “amino acid” refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to naturally occurring amino acids. Naturally occurring amino acids are amino acids that are encoded by the genetic code as well as later modified, such as hydroxy proline, γ-carboxyglutamate and O-phosphoserine. Amino acid analogs refer to compounds having the same basic chemical structure as naturally occurring amino acids, i.e., an α carbon bonded to a hydrogen, carboxyl group, amino group, and R group, such as homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. These analogs have modified R groups (eg, norleucine) or modified peptide backbones, but retain the same basic chemical structure as naturally occurring amino acids. Amino acid mimetics refer to compounds that have a structure that differs from the normal chemical structure of amino acids, but function in a manner similar to natural amino acids. The terms “non-naturally occurring amino acid” and “non-natural amino acid” refer to amino acid analogs, synthetic amino acids and amino acid mimetics that are not found in nature.

Amino acids may be referred to herein by either the commonly known three-letter symbols or the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Committee. Likewise, nucleotides may be referred to by their generally accepted single letter codes.

"Conservatively modified variants" apply to both amino acid and nucleic acid sequences. With respect to a particular nucleic acid sequence, "conservatively modified variants" refer to nucleic acids that encode identical or essentially identical amino acid sequences. Because of the degeneracy of the genetic code, many nucleic acid sequences will encode any given protein. For example, the codons GCA, GCC, GCG and GCU all code for the amino acid alanine. Thus, at any position where an alanine is specified by a codon, the codon can be changed to any corresponding codon described without altering the encoded polypeptide.

Such nucleic acid variances are "silent variances", which are a type of conservatively modified variance. Every nucleic acid sequence herein that encodes a polypeptide also describes all possible silent modifications of the nucleic acid. One skilled in the art will recognize that each codon in a nucleic acid (except for AUG, which is typically the only codon for methionine, and TGG, which is typically the only codon for tryptophan) can be modified to create a functionally identical molecule. Thus, each silent variation of a nucleic acid encoding a polypeptide is included in each sequence described.

With respect to amino acid sequences, one of ordinary skill in the art knows that individual substitutions, deletions or additions to nucleic acid, peptide, polypeptide or protein sequences altering, adding or deleting a single amino acid or a small percentage of encoded amino acids result in alterations in the sequence of amino acids that are chemically similar. It will be appreciated that "conservatively modified variants" are substituted with. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to, and do not exclude, the polymorphic variants, interspecies homologs and alleles of the present invention.

The following eight groups each contain amino acids that are conservative substitutions for each other: 1) Alanine (A), Glycine (G); 2) aspartic acid (D), glutamic acid (E); 3) asparagine (N), glutamine (Q); 4) arginine (R), lysine (K); 5) isoleucine (I), leucine (L), methionine (M), valine (V); 6) phenylalanine (F), tyrosine (Y), tryptophan (W); 7) serine (S), threonine (T); and 8) cysteine (C), methionine (M) (see, eg, Creighton, Proteins (1984)).

The term "identical" or "identity" in relation to two or more nucleic acid or polypeptide sequences means that they are identical, or a specified percentage as determined by manual alignment and visual inspection or using the BLAST or BLAST 2.0 sequence comparison algorithm using the default parameters described below. about 60% identity, preferably 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92 %, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater identity) refers to two or more identical sequences or subsequences having amino acid residues or nucleotides (e.g., NCBI website http see ://www.ncbi.nlm.nih.gov/BLAST/, etc.). Here, the sequences are said to be "substantially identical". This definition may also refer to or apply to the complement of a test sequence. The definition also includes sequences with deletions and/or additions as well as those with substitutions. As discussed below, preferred algorithms can account for gaps and the like. Preferably, the identity exists over a region that is at least about 25 amino acids or nucleotides in length, more preferably over a region that is 50 to 100 amino acids or nucleotides in length.

As used herein, the term "thymidine kinase gene", "TK gene", "TK", "J2R gene" or "J2R" refers to the activity of any recombinant or naturally occurring form of a thymidine kinase gene or thymidine kinase polypeptide. Encodes a thymidine kinase polypeptide capable of retaining (eg, within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity relative to a thymidine kinase polypeptide) refers to a variant or homolog thereof. In some embodiments, the variant or homolog is at least 90%, 95%, or more distinct over the entire sequence or a portion of the sequence (e.g., 50, 100, 150 or 200 contiguous nucleic acid segments) compared to a naturally occurring thymidine kinase gene. %, 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity. In an embodiment, the thymidine kinase gene is substantially identical to, or a variant or homolog that has substantial identity to, a nucleic acid sequence corresponding to positions 83422 to 83955 of the nucleic acid sequence identified by accession number DQ121394. In an embodiment, the thymidine kinase gene comprises the nucleic acid sequence of SEQ ID NO:4. In an embodiment, the thymidine kinase gene is the nucleic acid sequence of SEQ ID NO:4. In an embodiment, the thymidine kinase gene is mutated. In an embodiment, the thymidine kinase gene is partially deleted. In an embodiment, the thymidine kinase gene comprises the nucleic acid sequence of SEQ ID NO:5. In an embodiment, the thymidine kinase gene comprises the nucleic acid sequence of SEQ ID NO:5.

As used herein, the terms "F14.5L gene", "F14.5L sequence", "F14.5L" and the like refer to the activity of any recombinant or naturally occurring form of the F14.5L gene or F14.5L polypeptide (e.g. , a variant thereof encoding a F14.5L polypeptide capable of retaining within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity relative to the F14.5L polypeptide, or refers to homologues. In some embodiments, the variant or homolog is at least 90%, 95%, or more over the entire sequence or a portion of the sequence (e.g., 50, 100, 150 or 200 contiguous nucleic acid segments) compared to a naturally occurring F14.5L gene. %, 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity. In an embodiment, the F14.5L gene is substantially identical to, or a variant or homolog with substantial identity to, a nucleic acid sequence corresponding to positions 44428 to 44279 of the nucleic acid sequence identified by accession number KX781953. In an embodiment, the F14.5L gene comprises the nucleic acid sequence of SEQ ID NO:6. In an embodiment, the F14.5L gene is the nucleic acid sequence of SEQ ID NO:6. In an embodiment, the F14.5L gene is mutated. In an embodiment, the F14.5L gene gene is partially deleted. In an embodiment, the F14.5L gene comprises the nucleic acid sequence of SEQ ID NO:7. In an embodiment, the F14.5L gene comprises the nucleic acid sequence of SEQ ID NO:7.

As used herein, the terms "D4R gene", "uracil DNA glycosylase gene" and the like refer to the activity of any recombinant or naturally occurring form of a uracil DNA glycosylase gene or uracil DNA glycosylase polypeptide (e.g., uracil A variant thereof encoding a uracil DNA glycosylase capable of retaining within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity relative to a DNA glycosylase polypeptide. or homologues. In some embodiments, the variant or homolog is at least 90% over the entire sequence or a portion of the sequence (e.g., 50, 100, 150 or 200 contiguous nucleic acid segments) compared to a naturally occurring uracil DNA glycosylase gene. , 95%, 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity. In an embodiment, the DNA glycosylase gene is substantially identical to, or a variant or homolog with substantial identity to, a nucleic acid sequence corresponding to positions 102720 to 103376 of the nucleic acid sequence identified by accession number DQ439815. In an embodiment, the uracil DNA glycosylase gene comprises the nucleic acid sequence of SEQ ID NO:8. In an embodiment, the uracil DNA glycosylase gene is the nucleic acid sequence of SEQ ID NO:8.

As used herein, the terms "E9L gene", "DNA polymerase gene" and the like refer to the activity of any recombinant or naturally occurring form of a DNA polymerase gene or DNA polymerase polypeptide (e.g., at least relative to a DNA polymerase polypeptide). within 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity) that encodes a DNA polymerase polypeptide or a variant or homolog thereof. In some embodiments, the variant or homolog is at least 90%, 95%, or more distinct over the entire sequence or a portion of the sequence (e.g., 50, 100, 150 or 200 contiguous nucleic acid segments) compared to a naturally occurring DNA polymerase gene. %, 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity. In an embodiment, the DNA polymerase gene is substantially identical to, or a variant or homolog that has substantial identity to, a nucleic acid sequence corresponding to positions 56656 to 53636 of the nucleic acid sequence identified by accession number AY243312. In an embodiment, the DNA polymerase gene comprises the nucleic acid sequence of SEQ ID NO: 12. In an embodiment, the DNA polymerase gene is the nucleic acid sequence of SEQ ID NO: 12.

As used herein, the terms “human sodium iodide symporter gene”, “hNIS gene”, “NIS gene” and the like refer to any recombinant or naturally occurring form of the human sodium iodide symporter gene or human sodium iodide symporter gene. retain the activity of the transporter polypeptide (e.g., within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to a human sodium iodine cotransporter gene polypeptide) Refers to a variant or homologue thereof that encodes a human sodium iodine symporter polypeptide that can be capable of. e.g., at least 90%, 95%, 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity over 50, 100, 150 or 200 contiguous nucleic acid segments. The iodine symporter gene is substantially identical to, or a variant or homologue having substantial identity to, the nucleic acid sequence identified as accession number NM_000453 In an embodiment, the human sodium iodine symporter gene comprises the nucleic acid sequence of SEQ ID NO: 13. In an embodiment, the human sodium iodine cotransporter gene is the nucleic acid sequence of SEQ ID NO: 13.

As used herein, the term "emerald gene", "emerald sequence" refers to the activity of an emerald polypeptide (e.g., at least 50%, 80%, 90%, 95%, 96%, 97%, 98% relative to an emerald polypeptide). , within 99% or 100% activity) refers to a genetically engineered gene or variant thereof encoding an emerald polypeptide. In some embodiments, the variant or homolog is at least 90%, 95%, or more over the entire sequence or a portion of the sequence (e.g., 50, 100, 150 or 200 contiguous nucleic acid segments) compared to a naturally occurring emerald sequence. have 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity. In an embodiment, the emerald gene is substantially identical to, or a variant or homolog having substantial identity to, a nucleic acid sequence corresponding to positions 3215 to 3931 of the nucleic acid sequence identified by accession number KF293661. In an embodiment, the emerald gene comprises the nucleic acid sequence of SEQ ID NO: 14. In an embodiment, the emerald gene is the nucleic acid sequence of SEQ ID NO: 14.

As used herein, the terms “firefly luciferase gene” and “firefly luciferase sequence” refer to the activity of any recombinant or naturally occurring form of a firefly luciferase gene or firefly luciferase polypeptide (e.g., relative to a firefly luciferase polypeptide). refers to a variant or homolog thereof that encodes a firefly luciferase polypeptide capable of retaining within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity. In some embodiments, the variant or homologue is at least 90%, 95%, or more over the entire sequence or a portion of the sequence (e.g., 50, 100, 150 or 200 contiguous nucleic acid segments) compared to a naturally occurring firefly luciferase gene. %, 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity. In an embodiment, the firefly luciferase gene is substantially identical to, or a variant or homolog with substantial identity to, a nucleic acid sequence corresponding to positions 3129 to 4781 of the nucleic acid sequence identified by accession number KF990214. In an embodiment, the firefly luciferase gene comprises the nucleic acid sequence of SEQ ID NO: 15. In an embodiment, the firefly luciferase gene is the nucleic acid sequence of SEQ ID NO: 15.

As used herein, the term "mCherry gene", "mCherry sequence" refers to the activity of any recombinant or naturally occurring form of mCherry gene or mCherry polypeptide (e.g., at least 50% relative to mCherry polypeptide). %, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some embodiments, the variant or homolog is at least 90%, 95% over the entire sequence or a portion of the sequence (e.g., 50, 100, 150 or 200 contiguous nucleic acid segments) compared to a naturally occurring m.cheri gene. , 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity. In an embodiment, the M.cheri gene is substantially identical to, or a variant or homolog having substantial identity to, a nucleic acid sequence corresponding to positions 1073 to 1783 of the nucleic acid sequence identified by accession number KX446949. In an embodiment, the mcheri gene comprises the nucleic acid sequence of SEQ ID NO: 16. In an embodiment, the mcheri gene is the nucleic acid sequence of SEQ ID NO: 16.

As used herein, the terms "H5 promoter", "H5" and the like refer to any recombinant or naturally occurring form of the H5 promoter or the activity of the H5 promoter (e.g., at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity) refers to variants or homologs thereof that encode the H5 promoter. In some embodiments, the variant or homolog is at least 90%, 95%, 95%, have 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity. In an embodiment, the H5 promoter is substantially identical to, or a variant or homolog having substantial identity to, a nucleic acid sequence corresponding to positions 7-76 of the nucleic acid sequence identified by accession number FJ386852. In an embodiment, the H5 promoter comprises the nucleic acid sequence of SEQ ID NO: 18. In an embodiment, the H5 promoter is the nucleic acid sequence of SEQ ID NO: 18.

As used herein, the terms "SE promoter", "SE" and the like refer to any recombinant or naturally occurring form of an SE promoter or the activity of an SE promoter (e.g., at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity) refers to variants or homologues thereof that encode the SE promoter. In some embodiments, the variant or homolog is at least 90%, 95%, 95%, or more over the entire sequence or a portion of the sequence (e.g., 50, 100, 150 or 200 contiguous nucleic acid segments) compared to a naturally occurring SE promoter. have 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity. In an embodiment, the SE promoter comprises the nucleic acid sequence of SEQ ID NO: 19. In an embodiment, the SE promoter is the nucleic acid sequence of SEQ ID NO: 19.

As used herein, the terms “11K promoter”, “11K” and the like refer to any recombinant or naturally occurring form of an 11K promoter or an activity of an 11K promoter (e.g., at least 50%, 80%, 90%, within 95%, 96%, 97%, 98%, 99% or 100% activity). In some embodiments, the variant or homolog has at least 90%, 95%, have 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity. In an embodiment, the 11K promoter is substantially identical to, or a variant or homolog having substantial identity to, a nucleic acid sequence corresponding to positions 40734 to 40771 of the nucleic acid sequence identified by accession number KF179385. In an embodiment, the 11K promoter comprises the nucleic acid sequence of SEQ ID NO:20. In an embodiment, the 11K promoter is the nucleic acid sequence of SEQ ID NO:20.

Antibodies are large complex molecules (molecular weight of about 150,000 or about 1320 amino acids) with a complex internal structure. A native antibody molecule contains two identical pairs of polypeptide chains, each pair having one light chain and one heavy chain. Each light and heavy chain, in turn, consists of two regions: a variable ("V") region that is involved in binding target antigens and a constant ("C") region that interacts with other components of the immune system. The light chain and heavy chain variable regions are assembled in three-dimensional space to form a variable region that binds an antigen (eg, a receptor on the cell surface). Within each light or heavy chain variable region are three short segments (on average 10 amino acids in length) called complementarity determining regions (“CDRs”). The six CDRs (three from the light chain and three from the heavy chain) within the antibody variable domain fold together in three-dimensional space to form the actual antibody binding site that docks to the target antigen. The location and length of the CDRs are described in Kabat, E. et al., Sequences of Proteins of Immunological Interest, U.S. Department of Health and Human Services, 1983, 1987]. The part of the variable region not contained in the CDR is called the framework (“FR”) that forms the environment for the CDR.

The term "antibody" is used according to its commonly known meaning in the art. Antibodies exist, for example, as intact immunoglobulins or as a number of well-characterized fragments resulting from digestion with various peptidases. Thus, for example, pepsin cleaves the antibody below the disulfide bonds in the hinge region to yield F(ab)′ ₂ , a dimer of Fab, itself a light chain linked to V _H -C _H1 by a disulfide bond. do. F(ab)' ₂ can be reduced under mild conditions that break disulfide bonds in the hinge region, thereby converting F(ab)' ₂ dimers to Fab' monomers. A Fab' monomer is essentially a Fab with part of the hinge region (see Paul ed., 3d ed. 1993). Although various antibody fragments are defined in terms of degradation of intact antibodies, those skilled in the art will understand that such fragments may be synthesized de novo, either chemically or using recombinant DNA methodologies. Accordingly, the term antibody as used herein refers to antibody fragments generated by modification of whole antibodies or antibody fragments newly synthesized using recombinant DNA methodology (e.g., single-chain Fv) or antibody fragments identified using phage display libraries. (see, eg, McCafferty et al ., Nature 348: 552-554 (1990)).

The structural units of an exemplary immunoglobulin (antibody) include a tetramer. Each tetramer consists of two identical pairs of polypeptide chains, each pair having one "light chain" (about 25 kD) and one "heavy chain" (about 50 to 70 kD). The N-terminus of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms variable light chain (VL) and variable heavy chain (VH) refer to light and heavy chains, respectively. The Fc (ie, fragment crystallizable region) is the "base" or "tail" of an immunoglobulin and typically consists of two heavy chains providing either two or three constant domains, depending on the class of antibody. By binding to specific proteins, the Fc region ensures that each antibody generates an appropriate immune response against a given antigen. The Fc region also binds various cellular receptors such as Fc receptors and other immune molecules such as complement proteins.

The term “antigen” as provided herein refers to a molecule capable of binding to an antibody binding domain provided herein. An “antigen binding domain” as provided herein is a region of an antibody that binds an antigen (epitope). As noted above, an antigen binding domain generally consists of one constant domain and one variable domain of each of the heavy and light chains (VL, VH, CL and CH1, respectively). A paratope or antigen binding site is formed at the N-terminus of the antigen binding domain. The two variable domains of an antigen binding domain typically bind epitopes on an antigen.

Antibodies exist, for example, as intact immunoglobulins or as a number of well-characterized fragments resulting from digestion with various peptidases. Thus, for example, pepsin cleaves the antibody below the disulfide bonds in the hinge region to yield F(ab)'2, which is itself a dimer of Fab, a light chain linked to VH-CH1 by a disulfide bond. F(ab)'2 can be reduced under mild conditions that break disulfide bonds in the hinge region, thereby converting F(ab)'2 dimers to Fab' monomers. The Fab' monomer is essentially an antigen binding site with part of the hinge region (see Fundamental Immunology (Paul ed., 3d ed. 1993). Various antibody fragments have been defined in terms of degradation of intact antibodies; Those of ordinary skill in the art will understand that such fragments can be synthesized de novo chemically or using recombinant DNA methodology.Therefore, the term antibody as used herein refers to an antibody fragment produced by modification of a whole antibody, or de novo using recombinant DNA. synthetic antibody fragments (e.g., single-chain Fv) or antibody fragments identified using phage display libraries (see, eg, McCafferty et al., Nature 348:552-554 (1990)). .

A single-chain variable fragment (scFv) is a fusion protein in which the variable regions of the heavy (VH) and light (VL) chains of an immunoglobulin are linked by a short linker peptide of 10 to about 25 amino acids. Linkers may be enriched in serine or threonine, usually for solubility, as well as glycine for flexibility. A linker can connect the N-terminus of VH to the C-terminus of VL or vice versa.

The epitope of an antibody is the region of the antigen to which the antibody binds. If two antibodies competitively inhibit (block) the binding of the other antibody to the antigen, they bind to the same or overlapping epitope. In other words, when measured in a competitive binding assay, a 1x, 5x, 10x, 20x or 100x excess of one antibody reduces the binding of the other antibody by at least 30%, but preferably by 50%, 75%, 90% or even 99%. % (see, eg, Junghans et al ., Cancer Res. 50:1495, 1990). Alternatively, two antibodies have the same epitope if essentially all amino acid mutations in the antigen that reduce or eliminate binding of one antibody reduce or eliminate binding of the other antibody. If some amino acid mutation that reduces or eliminates binding of one antibody reduces or eliminates binding of the other antibody, the two antibodies have overlapping epitopes.

For the preparation of suitable antibodies of the present invention and for use according to the present invention, many techniques known in the art can be used, for example recombinant monoclonal or polyclonal antibodies (see, for example, Kohler & Milstein, Nature 256 :495-497 (1975) Kozbor et al., Immunology Today 4: 72 (1983) Cole et al., pp. 77-96 in Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc. (1985); Coligan, Current Protocols in Immunology (1991); Harlow & Lane, Antibodies, A Laboratory Manual (1988); and Goding, Monoclonal Antibodies: Principles and Practice (2d ed. 1986)). Genes encoding the heavy and light chains of the antibody of interest can be cloned from cells. For example, a gene encoding a monoclonal antibody can be cloned from a hybridoma and used to produce a recombinant monoclonal antibody. In addition, a gene library encoding the heavy and light chains of monoclonal antibodies can be prepared from hybridomas or plasma cells. Heavy and light chain gene products are randomly combined to generate large pools of antibodies with different antigenic specificities (see, eg, Kuby, Immunology (3rd ed. 1997)). Antibodies to the polypeptides of the present invention can be produced by applying single-chain antibody or recombinant antibody production techniques (US Pat. No. 4,946,778, US Pat. No. 4,816,567). In addition, other organisms such as transgenic mice or other mammals can be used to express humanized or human antibodies (see, e.g., U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; , No. 5,661,016, Marks et al., Bio/Technology 10:779-783 (1992); Lonberg et al., Nature 368:856-859 (1994); Morrison, Nature 368:812-13 (1994) See also Fishwild et al., Nature Biotechnology 14:845-51 (1996); Neuberger, Nature Biotechnology 14:826 (1996); and Lonberg & Huszar, Intern. Rev. Immunol. 13:65-93 (1995)). . Alternatively, phage display technology can be used to identify antibodies and heteromeric Fab fragments that specifically bind to a selected antigen (see, eg, McCafferty et al., Nature 348:552-554 (1990)). ; Marks et al., Biotechnology 10:779-783 (1992)). Antibodies can also be made bispecific, i.e. capable of recognizing two different antigens (eg WO 93/08829, Traunecker et al., EMBO J. 10:3655-3659 (1991) and Suresh et al., Methods in Enzymology 121:210 (1986)). Antibodies can also be heteroconjugates, such as two covalently linked antibodies or immunotoxins (see, eg, US Pat. No. 4,676,980, WO 91/00360, WO 92/200373 and EP 03089).

When referring to a protein or peptide, the phrases "specifically (or selectively) binds to an antibody" or "specifically (or selectively) immunoreacts to" often refer to the expression of a protein in a heterogeneous population of proteins and other biologics. It refers to the bonding reaction that determines existence. Thus, under designated immunoassay conditions, the specified antibody binds to a particular protein at least twice background, more typically 10 to 100 times greater than background. Specific binding to the antibody under these conditions typically requires the antibody to be selected for specificity to a particular protein. For example, polyclonal antibodies may be selected to obtain only a subset of antibodies that specifically immunoreact with a selected antigen and do not specifically immunoreact with other proteins. This selection can be achieved by excluding antibodies that cross-react with other molecules. Various immunoassays can be used to select antibodies that specifically immunoreact with a specific protein. For example, solid phase ELISA immunoassays are commonly used to screen for antibodies that specifically immunoreact with a protein (see, e.g., Harlow & Lane, Using Antibodies, A Laboratory Manual (1998) for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity]).

"Contacting" is used according to its ordinary and conventional meaning, and is the process of bringing at least two distinct species (e.g., biomolecules or chemical compounds comprising cells) into close enough proximity for a reaction, interaction, or physical contact. means However, it should be understood that the resulting reaction product may result directly from the reaction between the added reagents or from an intermediate that may result in the reaction mixture from one or more of the added reagents.

The term "contacting" may include bringing two species into reaction, interaction, or physical contact, where the two species may be, for example, an antibody domain and an antibody binding domain described herein. In embodiments contacting comprises, for example, allowing an antibody domain described herein to interact with an antibody binding domain.

“Patient” or “subject in need thereof” refers to a living organism suffering from or susceptible to a disease or condition that can be treated by administration of a composition or pharmaceutical composition provided herein. Non-limiting examples include humans, other mammals, cattle, rats, mice, dogs, monkeys, goats, sheep, cows, deer and other non-mammalian animals. In some embodiments, the patient is a human.

The term “disease” or “condition” refers to a condition or state of health in a patient or subject that can be treated with a compound or method provided herein. The disease may be cancer. In some further cases, "cancer" refers to human cancers and carcinomas, sarcomas, adenocarcinomas, leukemias including solid and lymphoid cancers, kidney cancer, breast cancer, lung cancer, bladder cancer, colon cancer, ovarian cancer, prostate cancer, pancreatic cancer, stomach cancer, Lymphoma, including brain cancer, head and neck cancer, cervical cancer, testicular cancer, glioma, esophageal cancer, and liver cancer, including hepatocarcinoma, type B acute lymphocytic lymphoma, non-Hodgkin's lymphoma (eg, Burkitt's, small cell and giant cell lymphoma), Hodgkin's lymphoma , leukemia (including AML, ALL and CML) or multiple myeloma.

As used herein, the term “cancer” refers to any type of cancer, neoplasm or malignant tumor found in mammals (eg humans), including leukemias, carcinomas and sarcomas. Exemplary cancers that can be treated with the compounds or methods provided herein include breast cancer, colorectal cancer, kidney cancer, leukemia, lung cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer, brain cancer, liver cancer, stomach cancer, or sarcoma.

The term "leukemia" broadly refers to a progressive malignant disease of the blood-forming organs and is generally characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemia is usually clinically (1) acute or chronic, depending on the duration and nature of the disease; (2) myeloid (myeloid), lymphoid (lymphoid), or mononuclear, depending on the type of cell involved; (3) It is classified as leukemia or aleukemia (subleukemia) according to the presence or absence of an increase in the number of normal cells in the blood. Exemplary leukemias that can be treated with the compounds or methods provided herein include, for example, acute nonlymphocytic leukemia, chronic lymphocytic leukemia, acute granulocytic leukemia, chronic granulocytic leukemia, acute promyelocytic leukemia, adult T cell leukemia , aleukemic leukemia, leukopenic leukemia, basophilic leukemia, blast cell leukemia, bovine leukemia, chronic myelocytic leukemia, cutaneous leukemia, embryonic leukemia, eosinophilic leukemia, gross leukemia, ciliary cell leukemia, hemoblastic leukemia, Hemoblastic leukemia, histiocytic leukemia, stem cell leukemia, acute monocytic leukemia, lymphopenic leukemia, lymphatic leukemia, lymphoblastic leukemia, lymphocytic leukemia, lymphogeneous leukemia, lymphoid ) leukemia, lymphosarcoma cell leukemia, mast cell leukemia, megakaryocyte leukemia, osteoblastic leukemia, monocytic leukemia, myeloblastic leukemia, myelocytic leukemia, myeloid granulocytic leukemia, myelomonocytic leukemia, Negeli leukemia, plasma cell leukemia, multiple myeloma, plasmacytic leukemia, promyelocytic leukemia, rider cell leukemia, Schilling leukemia, stem cell leukemia, subleukemia or undifferentiated cell leukemia.

The term “sarcoma” refers to a tumor composed of densely packed cells, usually composed of material such as embryonic connective tissue, usually embedded in a fibrous or homogeneous material. Sarcomas that can be treated with the compounds or methods provided herein include chondrosarcoma, fibrosarcoma, lymphosarcoma, melanosarcoma, myxosarcoma, osteosarcoma, Abemethy's sarcoma, adipose sarcoma (liposarcoma), acinar soft sarcoma. , enamel sarcoma, staphylococcal sarcoma, chlorophyll sarcoma, chorionic carcinoma, embryonic sarcoma, Wilms tumor sarcoma, endometrial sarcoma, stromal sarcoma, Ewing's sarcoma, myofascial sarcoma, fibroblast sarcoma, giant cell sarcoma, granulocyte sarcoma, Hodgkin's Sarcoma, idiopathic multifocal hemorrhagic sarcoma, B-cell immunoblastic sarcoma, lymphoma, T-cell immunoblastic lymphoma, Jensen's sarcoma, Kaposi's sarcoma, Kupffer's cell sarcoma, angiosarcoma, leukemia sarcoma, malignant mesenchymal sarcoma, parosteal sarcoma, reticular cell sarcoma, Rous sarcoma, serous cystic sarcoma, synovial sarcoma, or telangiectasia sarcoma.

The term “melanoma” is intended to mean tumors arising from the melanocyte system of the skin and other organs. Melanoma that can be treated with the compounds or methods provided herein include, for example, acromegaly lentiginous melanoma, amelanin melanoma, benign juvenile melanoma, Cloudman melanoma, S91 melanoma, Harding-Parsey melanoma, juvenile Includes melanoma, lentigo malignant melanoma, malignant melanoma, nodular melanoma, subungual melanoma or superficial diffuse melanoma.

The term “carcinoma” refers to a malignant new growth composed of epithelial cells that tend to infiltrate surrounding tissues and give rise to metastasis. Exemplary carcinomas that can be treated with the compounds or methods provided herein include, for example, medullary thyroid carcinoma, familial medullary thyroid carcinoma, acinar carcinoma, acinous carcinoma, adenocytic carcinoma. , adenoid cystic carcinoma), adenocarcinoma (carcinoma adenomatosum), adrenocortical carcinoma, aveolar carcinoma, aveolar cell carcinoma, basal cell carcinoma (carcinoma basocellulare), basal-like carcinoma, basal squamous cell carcinoma, bronchioloalveolar carcinoma, bronchiolar carcinoma, bronchial carcinoma, cerebral carcinoma, cholangiocarcinoma, chorionic carcinoma, colloidal carcinoma, comedonoid carcinoma, cervical carcinoma, filamentous carcinoma, carcinoma en cuirasse, crustal carcinoma, cylindrical carcinoma, columnar cell carcinoma, ductal carcinoma, hard carcinoma, embryonic carcinoma, encephaloid carcinoma, epithelial carcinoma, carcinoma epitheliale adenoides, extrinsic carcinoma, ulcer etc. Carcinoma ex ulcere, carcinoma fibrosum, gelatiniforni carcinoma (gelatinous carcinoma), giant cell carcinoma (carcinoma gigantocellulare), glandular carcinoma, granulosa cell carcinoma cell carcinoma, hematoid carcinoma, hepatocellular carcinoma, hurthle cell carcinoma, hyaline carcinoma, hypernephroid carcinoma, infantile embryonic carcinoma embryonal carcinoma), carcinoma in situ, intraepidermal carcinoma, intraepithelial carcinoma, Krompecher's carcinoma, Kulchitzky-cell carcinoma, giant large-cell carcinoma, lenticular carcinoma; carcinoma lenticulare), lipomatous carcinoma, lymphoepithelial carcinoma, carcinoma medullare (medullary carcinoma), melanotic carcinoma, carcinoma molle, mucinous carcinoma ; carcinoma muciparum), carcinoma mucocellulare, mucoepidermoid carcinoma, mucous carcinoma (carcinoma mucosum; mucous carcinoma), carcinoma myxomatodes, nasopharyngeal carcinoma, oat cell carcinoma carcinoma), carcinoma ossificans, osteoid carcinoma, papillary carcinoma, periportal carcinoma, preinvasive carcinoma, prickle cell carcinoma, pool carcinoma (pultaceous carcinoma), renal cell carcinoma of the kidney, reserve cell carcinoma, carcinoma sarcomatodes, schneiderian carcinoma, scirrhous carcinoma, carcinoma scroti, ring cell carcinoma, carcinoma simplex, small cell carcinoma, solanoid carcinoma, spheroid cell carcinoma, spindle cell carcinoma, carcinoma spongiosum, squamous carcinoma, squamous cell carcinoma, string carcinoma, telangiectaticum (carcinoma telangiectodes), transitional cell carcinoma, nodular carcinoma (carcinoma tuberosum; tuberous carcinoma), verrucous carcinoma, and carcinoma villosum.

The term "related to" or "related to" in the context of a substance or substance activity or function associated with a disease (eg, cancer, asthma, ulcerative colitis, irritable bowel syndrome, arthritis, uveitis, pyoderma gangrenosum, or erythema nodosum) is caused (in whole or in part) by that substance or substance activity or function, or the symptoms of a disease are caused (in whole or in part) by that substance or substance activity or function.

As defined herein, the terms "immune checkpoint", "immune checkpoint protein" or "checkpoint protein" may be used interchangeably and modulate the duration and magnitude of a physiological immune response (e.g., sustained immune cell activation). It refers to a composition (molecule) capable of attenuating and/or eliminating, thereby regulating normal immune homeostasis. Immune checkpoint proteins can stimulate (increase) an immune response. In an embodiment, the checkpoint protein is a cellular receptor. Examples of stimulatory checkpoint molecules are members of the tumor necrosis factor (TNF) receptor superfamily, such as CD27, CD40, OX40, glucocorticoid-induced TNFR family related gene (GITR) and CD137), members of the B7-CD28 superfamily (eg, CD28 itself and the Inducible T-cell costimulator (ICOS)). Alternatively, an immune checkpoint protein may suppress (reduce) an immune response. Examples of inhibitory checkpoint molecules are adenosine A2A receptor (A2AR), B7-H3, B7-H4, BTLA, CTLA-4, indolamine 2,3-dioxygenase (IDO), killer immunoglobulin-like receptor (KIR) immunoglobulin-like receptor), LAG3, PD-1, TIM-3, and V-domain immunoglobulin suppressor of T-cell activation (VISTA) protein.

Similarly, an "immune checkpoint inhibitor" or "checkpoint inhibitor" provided herein will inhibit, negatively affect (reduce) the activity or function of a checkpoint protein relative to the activity or function of the checkpoint protein in the absence of the inhibitor. refers to a substance (eg, an antibody or fragment thereof, a small molecule) capable of (eg, reducing the expression of or reducing the activity of a checkpoint protein). A checkpoint inhibitor at least partially, partially, or completely blocks stimulation of a checkpoint protein, reduces, prevents or delays activation of a checkpoint protein, or inactivates, desensitizes, or activates a checkpoint protein's signal transduction or enzymatic activity. Alternatively, the amount of the checkpoint protein can be down-regulated. A checkpoint inhibitor can inhibit a checkpoint protein by binding to it or by partially or completely blocking, reducing, preventing, delaying, inactivating, desensitizing, or down-regulating the activity of the checkpoint protein. In an embodiment, the checkpoint inhibitor is an antibody. In an embodiment, the checkpoint inhibitor is an antibody fragment. In an embodiment, the checkpoint inhibitor is an antibody variant. In an embodiment, the checkpoint inhibitor is a scFv. In an embodiment, the checkpoint inhibitor is an anti-CTLA-4 antibody. In an embodiment, the checkpoint inhibitor is an anti-PD1 antibody. In an embodiment, the checkpoint inhibitor is an anti-PD-L1 antibody. In an embodiment, the checkpoint inhibitor is an anti-LAG-3 antibody. In an embodiment, the checkpoint inhibitor is an anti-IgG1k antibody. In an embodiment, the checkpoint inhibitor is an anti-CD25 antibody. In an embodiment, the checkpoint inhibitor is an anti-IL2R antibody. In an embodiment, the checkpoint inhibitor forms part of an oncolytic virus. Non-limiting examples of checkpoint inhibitors include ipilimumab, pembrolizumab, nivolumab, talimogen laherparebec, duvalumab, daclizumab, avelumab and atezolimab.

As used herein, the term “abnormal” means different from normal. Abnormality, when used to describe enzyme activity, means an activity that is greater or less than the average of normal control or normal, non-diseased control samples. Aberrant activity can refer to an amount of an activity that results in a disease, wherein returning the aberrant activity to a normal or non-disease-related amount (eg, by using a method described herein) reduces the disease or one or more disease symptoms. causes

A "control" or "standard control" refers to a sample, measurement or value used as a standard, commonly known standard, for comparison with a test sample, measurement or value. For example, a test sample can be taken from a patient suspected of having a given disease (eg, cancer) and compared to a known normal (non-diseased) subject (eg, a standard control subject). A standard control is an average collected from a population of similar individuals (eg, standard control subjects) without a given disease (eg, healthy individuals of similar medical background, same age, weight, etc.) It can also represent a measurement or value. A standard control value can also be obtained from a sample obtained earlier from the same individual, eg, from a patient before onset of disease. For example, a control group can be designed to compare treatment effects based on pharmacological data (eg, half-life) or treatment regimen (eg, comparison of side effects). Controls are also important in determining the significance of the data. For example, if the value for a given parameter varies widely in the control group, the variation in the test sample will be considered insignificant. Many parameters (e.g., RNA levels, protein levels, specific cell types, specific body fluids, specific tissues, synovial cells, synovial fluid, synovial tissue, fibroblast-like synovial cells, macrophage-like synovial cells, etc.) It will be appreciated that it can be designed for the evaluation of

One skilled in the art will understand which standard control is most appropriate in a given situation and analyze data based on comparison to standard control values. Standard controls are also useful for determining the significance (eg, statistical significance) of data. For example, if the value of a given parameter varies widely in a standard control group, the variation in the test sample will be considered insignificant.

The term “diagnosis” refers to the relative probability that a disease (eg, cancer) is present in a subject. Similarly, the term “prognosis” refers to the relative probability that a particular future outcome will occur in an individual in relation to a disease state. For example, in the context of the present invention, prognosis can refer to the likelihood that an individual will develop a disease (eg, cancer) or possible severity of the disease (eg, duration of the disease). These terms are not intended to be absolute, as will be appreciated by those skilled in the art of medical diagnostics.

A “biological sample” or “sample” refers to material obtained from or derived from a subject or patient. Biological samples include tissue sections such as biopsy and autopsy samples and frozen sections used for histological purposes. Such samples include bodily fluids, such as blood and blood fractions or products (eg, serum, plasma, platelets, red blood cells, etc.), sputum, tissues, cultured cells (eg, primary cultures, grafts, and transformed cells). cells), feces, urine, synovial fluid, joint tissue, synovial tissue, synovial cells. fibroblast-like synovial cells, macrophage-like synovial cells, immune cells, hematopoietic cells, fibroblasts, macrophages, T cells, and the like. Biological samples are typically eukaryotic, eg mammals such as primates, eg chimpanzees or humans; cow; dog; cat; rodents such as guinea pigs, rats, mice; rabbit; or algae; reptile; or from fish.

As used herein, “cell” refers to a cell that performs metabolic or other functions sufficient to preserve or replicate its genomic DNA. Cells are known to be well known in the art, including, for example, the presence of intact membranes, staining with certain dyes, the ability to produce progeny or, in the case of germ cells, the ability to associate with a second gamete and produce viable progeny. method can be identified. Cells may include prokaryotic and eukaryotic cells. Prokaryotic cells include, but are not limited to, bacteria. Eukaryotic cells include, but are not limited to, yeast cells and cells of plant and animal origin, such as mammalian, insect (eg, spodoptera) and human cells. Cells may be useful if they are non-adherent in nature or have been treated to not adhere to a surface, for example by trypsinization.

The term "replication" is used according to its ordinary and conventional meaning and refers to the ability of a cell or virus to produce progeny. Those skilled in the art will readily understand that the term replication when used in reference to DNA refers to the biological process of producing two identical copies of DNA from one original DNA molecule. Thus, the term "cloning" includes the steps of passaging and reinfecting progeny cells. In an embodiment, a chimeric poxvirus provided herein exhibits increased oncolytic activity compared to its parent virus. In an embodiment, the oncolytic activity (ability to induce cell death in infected cells) is 1.5, 2, 3, 4 compared to the oncolytic activity of the parental virus (one of the viruses used to form the chimeric virus provided herein). , 5, 6, 7, 8, 9, 10, 100, 10000, increases over 10000 times.

As used herein, a "synergistic amount" is the sum of a first amount (eg, the amount of a first chimeric poxvirus) and a second amount (eg, the amount of a second chimeric poxvirus), such that a synergistic amount Refers to the amount that causes an action (ie, an effect greater than additive). Thus, the terms “synergy,” “synergism,” “synergistic,” “combined synergistic amount,” and “synergistic therapeutic effect,” as used interchangeably herein, mean that the measured effect is a single agent alone If it is greater than the sum of the individual effects of each chimeric poxvirus administered, it means the measured effect of the chimeric poxviruses administered in combination.

In an embodiment, the synergistic amount is about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3 of the amount of the first chimeric poxvirus when used separately from the second chimeric poxvirus. , 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8 , 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3 , 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8 , 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 , 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 , 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73 , 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 , or 99%. In an embodiment, the synergistic amount is about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3 of the amount of the second chimeric poxvirus when used separately from the first chimeric poxvirus. , 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8 , 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3 , 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8 , 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 , 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 , 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73 , 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 , or 99%.

The term “virus” or “viral particle” is used according to its normal and customary meaning within virology and refers to viral genomes (eg, DNA, RNA, single-stranded, double-stranded), viral capsids and related proteins, and in the case of enveloped viruses. (eg herpesvirus, poxvirus), a lipid and optionally a virion comprising an envelope comprising a component of the host cell membrane and/or viral proteins.

The term “poxvirus” is used according to its normal and customary meaning within virology and refers to a member of the poxviridae family that replicates in the cytoplasm of a host and is capable of infecting vertebrates and invertebrates. In an embodiment, a poxvirus virion is about 200 nm in diameter and about 300 nm in length and has a genome of a single, linear, double-stranded segment of DNA, typically between 130 and 375 kilobases. The term poxvirus includes, without limitation, all poxviride genus (e.g., betaentomopoxvirus, yatapoxvirus, cervidpoxvirus, gammaentomopoxvirus, gammaentomopoxvirus, leporipoxvirus, suipoxvirus, molluscipoxvirus, crocodylidpoxvirus, alphaentomopoxvirus, capripoxvirus, orthopox Viruses include avipoxvirus, and parapoxvirus In an embodiment, the poxvirus is an orthopoxvirus (eg, smallpox virus, vaccinia virus, vaccinia virus, monkeypox virus virus), parapox virus (e.g., pox virus, pseudopox virus, bovine popular stomatitis virus), yatapox virus (e.g. tanapox virus, yaba monkey) tumor virus) or molucipoxvirus (eg, molluscum contagiosum virus). In an embodiment, the poxvirus includes an orthopoxvirus (eg, vaccinia virus strain Brighton; Raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ledle-Jorman, or vaccinia virus strain AS) In an embodiment, the poxvirus is a parapoxvirus (eg, sheeppox virus strain NZ2 or pseudopox virus strain TJS).

The term “chimera,” as used in reference to poxviruses, is used according to its normal and customary meaning within virology and refers to two or more different microorganisms (e.g., two viruses of the same subfamily, two species of different subfamily). A hybrid microorganism (eg, a chimeric poxvirus) created by combining nucleic acid fragments from viruses of In an embodiment, nucleic acid fragments from two or more poxvirus strains combined contain essential genes necessary for replication. In an embodiment, a nucleic acid fragment from one of the two or more poxvirus strains contains essential genes necessary for replication. Chimeric poxviruses provided herein (including embodiments thereof) may include one or more transgenes (ie, nucleic acid sequences that are not unique to the viral genome). For example, a chimeric poxvirus (including embodiments thereof) provided herein may include an anti-cancer nucleic acid sequence, a nucleic acid binding sequence, a nucleic acid sequence encoding a detectable moiety, or any combination thereof. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence comprising an anti-cancer nucleic acid sequence, a nucleic acid binding sequence and a nucleic acid sequence encoding a detectable moiety. In an embodiment, a chimeric poxvirus comprises a nucleic acid sequence comprising an anti-cancer nucleic acid sequence and a nucleic acid sequence encoding a detectable moiety. In an embodiment, a chimeric poxvirus comprises a nucleic acid sequence comprising a nucleic acid binding sequence and a nucleic acid sequence encoding a detectable moiety. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence comprising an anti-cancer nucleic acid sequence and a nucleic acid binding sequence.

The term "plaque forming unit" is used according to its usual and customary meaning in virology and refers to the amount of plaque in a cell monolayer that can form per volume of viral particle. In some embodiments, units are based on the number of plaques that can form when infecting a monolayer of susceptible cells. For example, in an embodiment 1,000 PFU/μl indicates that 1 μl of a solution comprising viral particles contains enough viral particles to produce 1000 infectious plaques in a cell monolayer. In an embodiment, plaque forming units are abbreviated “PFU”.

The term "multiplicity of infection" or "MOI" is used according to its usual and customary meaning in virology and is the ratio of an infectious agent (eg poxvirus) to a target (eg cell) in a given area or volume. indicate In an embodiment, the area or volume is assumed to be uniform.

The term "Vaccinia virus strain Brighton" is used according to its ordinary and customary meaning and refers to virus strains of the same or similar designation and functional fragments and homologues thereof. The term refers to recombinant or naturally occurring forms of vaccinia virus strain Brighton or vaccinia virus strain Brighton activity (e.g., at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or within 100%). The term refers to a recombinant or naturally occurring form of vaccinia virus strain Brighton or its genome having sequence identity to the vaccinia virus strain Brighton genome (e.g., about 65%, 70%, 75%, 80%, 85% to vaccinia virus strain Brighton genome). , 90%, 95%, 99% or 100% identity). Vaccinia virus strain Brighton may refer to a variant having a mutated amino acid residue that modulates vaccinia virus strain Brighton activity, expression, cellular targeting, or infectivity (e.g., increased or decreased compared to vaccinia virus strain Brighton). Vaccinia virus strain Brighton can be modified as described herein. In an embodiment, vaccinia virus strain Brighton refers to a virus strain identified by ATCC (American Type Culture Collection) reference number ATCC VR-302™, variants or homologues thereof. In an embodiment, vaccinia virus strain Brighton refers to a virus strain identified by taxonomic reference number 265872, variants or homologues thereof.

The term "raccoon fox virus strain Herman" is used according to its ordinary and customary meaning and refers to virus strains with the same or similar designations and functional fragments and homologues thereof. The term refers to a recombinant or naturally occurring form of a raccoon fox virus strain Herman or a raccoon fox virus strain Herman activity (e.g., at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%). % or within 100%). The term refers to a recombinant or naturally occurring form of a raccoon fox virus strain herman or genome having sequence identity with the raccoon fox virus strain herman genome (e.g., about 65%, 70%, 75%, 80% to the raccoon fox virus strain herman genome). , 85%, 90%, 95%, 99% or 100% identity). Raccoon fox virus strain Herman will refer to a variant having a mutated amino acid residue that modulates (e.g., increases or decreases when compared to raccoon fox virus strain Herman) activity, expression, cellular targeting or infectivity of Raccoon fox virus strain Herman. can Raccoon fox virus strain Herman can be modified as described herein. In an embodiment, raccoon fox virus strain herman refers to a virus strain identified by ATCC reference number ATCC VR-838™, a variant or homolog thereof. In an embodiment, raccoon fox virus strain herman refers to a virus strain encoded by the nucleic acid sequence of reference number NC_027213.

The term “pox rabbit virus strain Utrecht” is used according to its normal and customary meaning and refers to virus strains with the same or similar designation and functional fragments and homologs thereof. The term refers to a recombinant or naturally occurring form of rabbitpox virus strain Utrecht or rabbitpox virus strain Utrecht activity (e.g., at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%). % or within 100%). The term refers to a recombinant or naturally occurring form of rabbitpox virus strain Utrecht or its genome having sequence identity to the rabbitpox virus strain Utrecht genome (e.g., about 65%, 70%, 75%, 80% to rabbitpox virus strain Utrecht genome). , 85%, 90%, 95%, 99% or 100% identity). Rabbitpox virus strain Utrecht may refer to a variant having a mutated amino acid residue that modulates rabbitpox virus strain Utrecht activity, expression, cellular targeting, or infectivity (e.g., increased or decreased when compared to rabbitpox virus strain Utrecht). there is. Rabbitpox virus strain Utrecht can be modified as described herein. In an embodiment, pox rabbit virus strain Utrecht refers to a virus strain identified by ATCC reference number ATCC VR-159™, variants or homologues thereof. In an embodiment, pox rabbit virus strain Utrecht refers to a virus strain identified by taxonomic reference number 45417, variants or homologs thereof.

The term "vaccinia virus strain WR" is used according to its ordinary and customary meaning and refers to virus strains with the same or similar designation and functional fragments and homologs thereof. The term refers to recombinant or naturally occurring forms of vaccinia virus strain WR or vaccinia virus strain WR activity (e.g., at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%). % or within 100%). The term refers to a recombinant or naturally occurring form of vaccinia virus strain WR or its genome having sequence identity to the vaccinia virus strain WR genome (e.g., about 65%, 70%, 75%, 80% to vaccinia virus strain WR genome). , 85%, 90%, 95%, 99% or 100% identity). Vaccinia virus strain WR refers to a variant having a mutated amino acid residue that modulates vaccinia virus strain WR activity, expression, cellular targeting, or infectivity (e.g., increased or decreased compared to vaccinia virus strain WR). can Vaccinia virus strain WR can be modified as described herein. In an embodiment, vaccinia virus strain WR refers to a virus strain identified by ATCC reference number ATCC VR-1354™, a variant or homolog thereof. In an embodiment, vaccinia virus strain WR refers to a virus strain identified by taxonomic reference number 10254, a variant or homolog thereof.

The term "vaccinia virus strain IHD" is used according to its ordinary and customary meaning and refers to virus strains of the same or similar designation and functional fragments and homologues thereof. This term refers to recombinant or naturally occurring forms of vaccinia virus strain IHD or vaccinia virus strain IHD activity (e.g., at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%). % or within 100%). The term refers to a sequence identity of a recombinant or naturally occurring form of vaccinia virus strain IHD or genome to the vaccinia virus strain IHD genome (e.g., about 65%, 70%, 75%, 80% to vaccinia virus strain IHD genome). , 85%, 90%, 95%, 99% or 100% identity). Vaccinia virus strain IHD will refer to a variant having a mutated amino acid residue that modulates vaccinia virus strain IHD activity, expression, cellular targeting or infectivity (eg, increased or decreased when compared to vaccinia virus strain IHD). can Vaccinia virus strain IHD can be modified as described herein. In an embodiment, vaccinia virus strain IHD refers to a virus strain identified by ATCC reference number ATCC VR-156™, a variant or homolog thereof. In an embodiment, vaccinia virus strain IHD refers to a virus strain identified by taxonomic reference number 10251, variants or homologues thereof.

The term "vaccinia virus strain Elstri" is used according to its ordinary and customary meaning and refers to virus strains of the same or similar designation and functional fragments and homologues thereof. The term refers to recombinant or naturally occurring forms of vaccinia virus strain Elstri or vaccinia virus strain Elstri activity (e.g., at least 30%, 40%, 50%, 60%, 70%, 80%, 90%). , within 95% or 100%). The term means that a recombinant or naturally occurring form of vaccinia virus strain Elstri or its genome has sequence identity to the vaccinia virus strain Elstri genome (e.g., about 65%, 70%, 75% to vaccinia virus strain Elstri genome). , 80%, 85%, 90%, 95%, 99% or 100% identity). Vaccinia virus strain Elstri refers to variants having mutated amino acid residues that modulate (e.g., increase or decrease when compared to vaccinia virus strain Elstri) activity, expression, cell targeting or infectivity of vaccinia virus strain Elstri. can do. Vaccinia virus strain Elstree can be modified as described herein. In an embodiment, vaccinia virus strain Elstri refers to a virus strain identified by ATCC reference number ATCC VR-1549™, variants or homologs thereof.

The term "vaccinia virus strain CL" is used according to its ordinary and customary meaning and refers to virus strains with the same or similar designation and functional fragments and homologues thereof. This term refers to recombinant or naturally occurring forms of vaccinia virus strain CL or vaccinia virus strain CL activity (e.g., at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%). % or within 100%). The term refers to a recombinant or naturally occurring form of vaccinia virus strain CL or its genome having sequence identity to the vaccinia virus strain CL genome (e.g., about 65%, 70%, 75%, 80% to vaccinia virus strain CL genome). , 85%, 90%, 95%, 99% or 100% identity). Vaccinia virus strain CL will refer to a variant having a mutated amino acid residue that modulates vaccinia virus strain CL activity, expression, cellular targeting or infectivity (eg, increased or decreased compared to vaccinia virus strain CL). can Vaccinia virus strain CL can be modified as described herein. In an embodiment, vaccinia virus strain CL refers to a virus strain identified by ATCC reference number ATCC VR-1774™, a variant or homolog thereof.

The term “vaccinia virus strain Ledle-Claudia” is used according to its ordinary and customary meaning and refers to virus strains of the same or similar designation and functional fragments and homologues thereof. The term refers to a recombinant or naturally occurring form of a vaccinia virus strain Reddlet-Illanobacteria or a vaccinia virus strain Redlet-Illoameric activity (e.g., at least 30%, 40%, 50%, 60%, 70% , within 80%, 90%, 95% or 100%). The term refers to the sequence identity of a recombinant or naturally occurring form of the vaccinia virus strain Ledle-Pelto or genome with the vaccinia virus strain Ledlé-Pelon genome (e.g., with the vaccinia virus strain Ledle-Pole genome). about 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% identity). The vaccinia virus strain Ledle-Pelorax modulates the activity, expression, cell targeting or infectivity of vaccinia virus strain Ledle-Pelora (e.g., increases or decreases when compared to vaccinia virus strain Ledla-Pelora). ) can refer to variants with mutated amino acid residues. The vaccinia virus strain Ledle-Panoramic can be modified as described herein. In an embodiment, the vaccinia virus strain Ledle-Panoramic refers to a virus strain identified by ATCC reference number ATCC VR-118™, a variant or homolog thereof.

The term "vaccinia virus strain AS" is used according to its ordinary and customary meaning and refers to virus strains with the same or similar designations and functional fragments and homologues thereof. This term refers to recombinant or naturally occurring forms of vaccinia virus strain AS or vaccinia virus strain AS activity (e.g., at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%). % or within 100%). The term refers to a recombinant or naturally occurring form of vaccinia virus strain AS or its genome having sequence identity to the vaccinia virus strain AS genome (e.g., about 65%, 70%, 75%, 80% to vaccinia virus strain AS genome). , 85%, 90%, 95%, 99% or 100% identity). Vaccinia virus strain AS will refer to a variant having a mutated amino acid residue that modulates vaccinia virus strain AS activity, expression, cell targeting or infectivity (eg, increased or decreased compared to vaccinia virus strain AS). can Vaccinia virus strain AS can be modified as described herein. In an embodiment, vaccinia virus strain AS refers to a virus strain identified by ATCC reference number ATCC VR-2010™, a variant or homolog thereof.

The term "sheeppox virus strain NZ2" is used according to its ordinary and customary meaning and refers to virus strains with the same or similar designation and functional fragments and homologues thereof. The term refers to recombinant or naturally occurring forms of sheeppox virus strain NZ2 or sheeppox virus strain NZ2 activity (e.g., at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or within 100%). The term refers to a recombinant or naturally occurring form of sheeppox virus strain NZ2 or a genome having sequence identity to the sheeppox virus strain NZ2 genome (e.g., about 65%, 70%, 75%, 80%, 85% to the sheeppox virus strain NZ2 genome). , 90%, 95%, 99% or 100% identity). The sheeppox virus strain NZ2 may refer to a variant having a mutated amino acid residue that modulates sheeppox virus strain NZ2 activity, expression, cellular targeting or infectivity (e.g., increased or decreased when compared to sheeppox virus strain NZ2). Both pox virus strain NZ2 can be modified as described herein. In an embodiment, sheeppox virus strain NZ2 refers to a viral strain identified by ATCC reference number ATCC VR-1548™, a variant or homolog thereof. In an embodiment, sheeppox virus strain NZ2 refers to a viral strain identified by taxonomic reference number 10259, variants or homologues thereof.

The term "pseudo vaccinia virus strain TJS" is used according to its ordinary and customary meaning and refers to a virus strain with the same or similar designation and functional fragments and homologues thereof. This term refers to recombinant or naturally occurring forms of pseudovax virus strain TJS or pseudovax virus strain TJS activity (e.g., at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%). % or within 100%). The term refers to cases in which the recombinant or naturally occurring form of pseudo vaccinia virus strain TJS or its genome has sequence identity to the pseudo vaccinia virus strain TJS genome (e.g., about 65%, 70%, 75%, 80% to pseudo vaccinia strain TJS genome). , 85%, 90%, 95%, 99% or 100% identity). Pseudopox virus strain TJS will refer to a variant having a mutated amino acid residue that modulates (e.g., increases or decreases when compared to pseudo vaccinia virus strain TJS) activity, expression, cellular targeting or infectivity of pseudo vaccinia virus strain TJS. can The pseudovax virus strain TJS can be modified as described herein. In an embodiment, pseudo vaccinia virus strain TJS refers to a viral strain identified by ATCC reference number ATCC VR-634™, variants or homologs thereof.

In an embodiment, the vaccinia virus strain Brighton is vaccinia virus strain Brighton ATCC VR-302™. In an embodiment, the raccoon fox virus strain Herman is the raccoon fox virus strain Herman ATCC VR-838™. In an embodiment, the rabbitpox virus strain Utrecht is a rabbitpox virus strain Utrecht ATCC VR-1591™. In an embodiment, the vaccinia virus strain WR is vaccinia virus strain WR ATCC VR-1354™. In an embodiment, the vaccinia virus strain IHD is vaccinia virus strain IHD ATCC VR-156™. In an embodiment, the vaccinia virus strain Elstri is the vaccinia virus strain Elstri ATCC VR-1549™. In an embodiment, the vaccinia virus strain CL is vaccinia virus strain CL ATCC VR-1774™. In an embodiment, the vaccinia virus strain Radle-Elyotima is vaccinia virus strain Radle-Eliotima ATCC VR-118™. In an embodiment, the vaccinia virus strain AS is vaccinia virus strain AS ATCC VR-2010™. In an embodiment, the sheeppox virus strain NZ2 is the sheeppox virus strain NZ2 ATCC VR-1548™. In an embodiment, the pseudo vaccinia virus strain TJS is pseudo vaccinia virus strain TJS ATCC VR-634™. In an embodiment, vaccinia virus strain Brighton refers to a virus strain identified by taxonomic reference number 265872, variants or homologues thereof.

In the present invention, "comprises", "comprising", "containing", and "having" may have the meaning defined in US patent law, and "include" ", "including" and the like. “Consisting essentially of” or “consisting essentially of” likewise has the meaning defined in United States patent law, and the term is open-ended, provided that no basic or novel feature of what is recited is altered by the presence of more than that recited. allow for the presence of more, but exclude prior art embodiments.

II. virus composition

In one aspect, a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, wherein the nucleic acid sequence is a vaccinia virus strain Brighton, a raccoon fox virus strain Herman, a rabbitpox virus strain Utrecht , vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia virus strain Radle-Elora, vaccinia virus strain AS, sheeppox virus strain NZ2, and pseudopox virus A chimeric poxvirus comprising nucleic acid fragments from two or more poxvirus strains selected from the group comprising strain TJS is provided.

A chimeric poxvirus described herein may contain a transgene. As used herein, "transgene" refers to a nucleic acid sequence derived from the outside of a given cell, organism or virus. Therefore, the transgenes provided herein are not native to poxviruses or do not originate within poxviruses. A provided transgene may encode a protein or may be a non-coding nucleic acid sequence. A transgene provided herein may include an anticancer nucleic acid sequence (eg, a nucleic acid binding sequence and a nucleic acid sequence encoding a polypeptide useful for treating cancer) or a nucleic acid sequence encoding a detectable moiety. Thus, in an embodiment, a chimeric poxvirus described herein comprises one or more anti-cancer nucleic acid sequences or nucleic acid sequences encoding a detectable moiety. In an embodiment, a chimeric poxvirus described herein comprises one or more anti-cancer nucleic acid sequences and a nucleic acid sequence encoding a detectable moiety.

In an embodiment, the nucleic acid sequence has at least 71% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 72% or greater sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 73% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 74% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 75% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 76% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 77% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 78% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 79% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 80% sequence identity to SEQ ID NO:1.

In an embodiment, the nucleic acid sequence has at least 81% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 82% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 83% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 84% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 85% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 86% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 87% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 88% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 89% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 90% sequence identity to SEQ ID NO:1.

In an embodiment, the nucleic acid sequence has at least 91% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 92% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 93% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 94% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 95% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 96% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 97% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 98% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has at least 99% sequence identity to SEQ ID NO:1.

In an embodiment, the nucleic acid sequence has at least 71% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 72% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 73% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 74% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 75% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 76% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 77% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 78% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 79% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 80% sequence identity to SEQ ID NO:2.

In an embodiment, the nucleic acid sequence has at least 81% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 82% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 83% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 84% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 85% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 86% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 87% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 88% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 89% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 90% sequence identity with SEQ ID NO:2.

In an embodiment, the nucleic acid sequence has at least 91% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 92% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 93% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 94% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 95% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 96% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 97% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 98% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has at least 99% sequence identity to SEQ ID NO:2.

In an embodiment, the nucleic acid sequence has 71% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 72% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 73% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 74% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 75% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 76% sequence identity with SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 77% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 78% sequence identity with SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 79% sequence identity with SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 80% sequence identity to SEQ ID NO:1.

In an embodiment, the nucleic acid sequence has 81% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 82% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 83% sequence identity with SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 84% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 85% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 86% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 87% sequence identity with SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 88% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 89% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 90% sequence identity to SEQ ID NO:1.

In an embodiment, the nucleic acid sequence has 91% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 92% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 93% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 94% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 95% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 96% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 97% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 98% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has 99% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence is the sequence of SEQ ID NO:1.

In an embodiment, the nucleic acid sequence has 71% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 72% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 73% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 74% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 75% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 76% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 77% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 78% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 79% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 80% sequence identity to SEQ ID NO:2.

In an embodiment, the nucleic acid sequence has 81% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 82% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 83% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 84% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 85% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 86% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 87% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 88% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 89% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 90% sequence identity to SEQ ID NO:2.

In an embodiment, the nucleic acid sequence has 91% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 92% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 93% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 94% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 95% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 96% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 97% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 98% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has 99% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence is the sequence of SEQ ID NO:1.

In an embodiment, the nucleic acid sequence has about 71% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 72% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 73% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 74% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 75% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 76% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 77% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 78% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 79% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 80% sequence identity to SEQ ID NO:1.

In an embodiment, the nucleic acid sequence has about 81% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 82% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 83% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 84% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 85% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 86% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 87% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 88% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 89% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 90% sequence identity to SEQ ID NO:1.

In an embodiment, the nucleic acid sequence has about 91% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 92% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 93% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 94% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 95% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 96% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 97% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 98% sequence identity to SEQ ID NO:1. In an embodiment, the nucleic acid sequence has about 99% sequence identity to SEQ ID NO:1.

In an embodiment, the nucleic acid sequence has about 71% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 72% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 73% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 74% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 75% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 76% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 77% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 78% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 79% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 80% sequence identity to SEQ ID NO:2.

In an embodiment, the nucleic acid sequence has about 81% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 82% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 83% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 84% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 85% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 86% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 87% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 88% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 89% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 90% sequence identity to SEQ ID NO:2.

In an embodiment, the nucleic acid sequence has about 91% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 92% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 93% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 94% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 95% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 96% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 97% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 98% sequence identity to SEQ ID NO:2. In an embodiment, the nucleic acid sequence has about 99% sequence identity to SEQ ID NO:2.

Nucleic acid sequences can have at least 70% sequence identity, and nucleic acid sequences with at least 70% sequence identity can be contiguous. In an embodiment, the nucleic acid sequences have at least 70% sequence identity and the nucleic acid sequences having at least 70% sequence identity are noncontiguous sequences. As provided herein, "non-contiguous sequence" refers to a sequence comprising one or more sequence fragments that do not have sequence identity with SEQ ID NO: 1 or SEQ ID NO: 2. In an embodiment, the non-contiguous sequence is SEQ ID NO: 1 or SEQ ID NO: 1 linked to a second sequence having at least 70% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2 via a sequence fragment having no sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2; A sequence comprising a first sequence fragment having at least 70% sequence identity with SEQ ID NO:2. In an embodiment, the non-contiguous sequence comprises a plurality of sequence fragments having at least 70% sequence identity with SEQ ID NO: 1 or SEQ ID NO: 2 linked through a plurality of sequence fragments having no sequence identity with SEQ ID NO: 1 or SEQ ID NO: 2. sequence that contains In an embodiment, the chimeric poxvirus further comprises a nucleotide insertion, deletion or mutation.

In an embodiment, the nucleic acid fragments are vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbitpox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia It is derived from the nia virus strain Ledle-Pyanobacteria and the vaccinia virus strain AS.

In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Brighton and raccoon fox virus strain Herman. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Brighton and harepox virus strain Utrecht. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Brighton and vaccinia virus strain WR. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Brighton and vaccinia virus strain IHD. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Brighton and vaccinia virus strain Elstree. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Brighton and vaccinia virus strain CL. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Brighton and vaccinia virus strain Ledle-Panoma. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Brighton and vaccinia virus strain AS. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Brighton and sheeppox virus strain NZ2. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Brighton and pseudovax virus strain TJS.

In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from pox virus strain Utrecht and vaccinia virus strain WR. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from rabbitpox virus strain Utrecht and vaccinia virus strain IHD. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from rabbitpox virus strain Utrecht and vaccinia virus strain Elstree. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from rabbitpox virus strain Utrecht and vaccinia virus strain CL. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from rabbitpox virus strain Utrecht and vaccinia virus strain Ledle-Panoma. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from rabbitpox virus strain Utrecht and vaccinia virus strain AS. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from rabbitpox virus strain Utrecht and sheeppox virus strain NZ2. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from rabbitpox virus strain Utrecht and pseudo vaccinia virus strain TJS.

In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain WR and vaccinia virus strain IHD. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain WR and vaccinia virus strain Elstree. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain WR and vaccinia virus strain CL. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain WR and vaccinia virus strain Radle-Panoma. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain WR and vaccinia virus strain AS. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain WR and sheeppox virus strain NZ2. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain WR and pseudovax virus strain TJS.

In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain IHD and vaccinia virus strain Elstree. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain IHD and vaccinia virus strain CL. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain IHD and vaccinia virus strain Radle-Panoma. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain IHD and vaccinia virus strain AS. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain IHD and sheeppox virus strain NZ2. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain IHD and pseudovax virus strain TJS.

In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Elstri and vaccinia virus strain CL. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strains Elstri and vaccinia virus strains Ledle-Panoramic. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Elstri and vaccinia virus strain AS. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Elstri and sheeppox virus strain NZ2. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Elstri and pseudovax virus strain TJS.

In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain CL and vaccinia virus strain Radle-Panoramia. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain CL and vaccinia virus strain AS. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain CL and sheeppox virus strain NZ2. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain CL and pseudovax virus strain TJS.

In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Ledle-Panoma and vaccinia virus strain AS. In an embodiment, the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Ledle-Elora and sheeppox virus strain NZ2. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain Ledle-Elora and pseudovax virus strain TJS.

In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain AS and sheeppox virus strain NZ2. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain AS and pseudovax virus strain TJS. In an embodiment, the nucleic acid sequence comprises nucleic acid fragments from vaccinia virus strain NZ2 and pseudo vaccinia virus strain TJS.

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus It includes nucleic acid fragments from strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Panoramic or vaccinia virus strain AS. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus It includes nucleic acid fragments from strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Panoma and vaccinia virus strain AS.

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Brighton. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from Raccoonpox virus strain herman. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from rabbitpox virus strain Utrecht. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising a nucleic acid fragment from vaccinia virus strain WR. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain IHD. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Elstri. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain CL. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Radle-Pornosum or vaccinia virus strain AS. include

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 2, the nucleic acid sequence comprising nucleic acid fragments from sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises a nucleic acid fragment from sheeppox virus strain NZ2. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises a nucleic acid fragment from pseudovax virus strain TJS.

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus It includes nucleic acid fragments from strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Panoramic or vaccinia virus strain AS. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus It includes nucleic acid fragments from strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Panoma and vaccinia virus strain AS.

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising a nucleic acid fragment from vaccinia virus strain Brighton. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from Raccoonpox virus strain herman. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from rabbitpox virus strain Utrecht. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising a nucleic acid fragment from vaccinia virus strain WR. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain IHD. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Elstri. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain CL. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Radle-Panoramic or vaccinia virus strain AS. include

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 2, the nucleic acid sequence comprising nucleic acid fragments from sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 2, wherein said nucleic acid sequence comprises a nucleic acid fragment from sheeppox virus strain NZ2. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 2, wherein said nucleic acid sequence comprises a nucleic acid fragment from pseudo vaccinia virus strain TJS.

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus It includes nucleic acid fragments from strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Panoramic or vaccinia virus strain AS. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus It includes nucleic acid fragments from strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Panoma and vaccinia virus strain AS.

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Brighton. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from Raccoonpox virus strain herman. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from rabbitpox virus strain Utrecht. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain WR. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain IHD. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Elstri. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain CL. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Radle-Pornosum or vaccinia virus strain AS. include

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 2, the nucleic acid sequence comprising nucleic acid fragments from sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises a nucleic acid fragment from sheeppox virus strain NZ2. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 90% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises a nucleic acid fragment from pseudovax virus strain TJS.

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus It includes nucleic acid fragments from strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Panoramic or vaccinia virus strain AS. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus It includes nucleic acid fragments from strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Panoma and vaccinia virus strain AS.

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Brighton. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from Raccoonpox virus strain herman. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from rabbitpox virus strain Utrecht. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising a nucleic acid fragment from vaccinia virus strain WR. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain IHD. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Elstri. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain CL. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Radle-Pornosum or vaccinia virus strain AS. include

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises nucleic acid fragments from sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises a nucleic acid fragment from sheeppox virus strain NZ2. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises a nucleic acid fragment from pseudovax virus strain TJS.

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus It includes nucleic acid fragments from strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Panoramic or vaccinia virus strain AS. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus It includes nucleic acid fragments from strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Panoma and vaccinia virus strain AS.

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Brighton. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from Raccoonpox virus strain herman. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from rabbitpox virus strain Utrecht. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain WR. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain IHD. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Elstri. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 1, said nucleic acid sequence comprising a nucleic acid fragment from vaccinia virus strain CL. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises a nucleic acid fragment from vaccinia virus strain Radle-Pornosum or vaccinia virus strain AS. include

In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 2, the nucleic acid sequence comprising nucleic acid fragments from sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises a nucleic acid fragment from sheeppox virus strain NZ2. In an embodiment, the chimeric poxvirus comprises a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises a nucleic acid fragment from pseudovax virus strain TJS.

In an embodiment, the chimeric poxvirus is an oncolytic virus. As used herein, an oncolytic virus is a virus capable of targeting and eliminating cancer cells. In an embodiment, the oncolytic virus targets lung cancer cells. In an embodiment, the oncolytic virus targets ovarian cancer cells. In an embodiment, the oncolytic virus targets pancreatic cancer cells. In an embodiment, the oncolytic virus preferentially targets cancer cells over non-cancer cells.

In an embodiment, the miRNA binding sequence forms part of the DNA polymerase gene of the chimeric poxvirus. In an embodiment, the poxvirus comprises a miRNA binding sequence. In an embodiment, the poxvirus comprises multiple miRNA binding sequences. In an embodiment, the plurality of miRNA binding sequences are independently different. In an embodiment, the plurality of miRNA binding sequences are identical. In an embodiment, the miRNA binding sequence is about 22 nucleotides in length. In an embodiment, the miRNA binding sequence is at least 22 nucleotides in length. In an embodiment, the miRNA binding sequence is 22 nucleotides in length. In an embodiment, the miRNA binding sequence is about 22 nucleotides in length. In an embodiment, each of the plurality of miRNA binding sequences is at least 22 nucleotides. In an embodiment, each of the plurality of miRNA binding sequences is about 22 nucleotides in length. In an embodiment, each of the plurality of miRNA binding sequences is 22 nucleotides.

In one aspect, an isolated nucleic acid encoding a chimeric poxvirus described herein is provided. In an embodiment, the isolated nucleic acid is SEQ ID NO: 1. In an embodiment, the isolated nucleic acid is SEQ ID NO:2.

III. Viral Compositions Containing Transgenes

Chimeric poxviruses (including embodiments thereof) provided herein may include a transgene. The transgene contained in the chimeric poxvirus provided herein can increase the oncolytic activity of the chimeric poxvirus compared to the chimeric poxvirus without the transgene. The transgene may further increase the ability of the chimeric poxvirus to differentially express/replicate in cancer cells compared to healthy (non-cancerous) cells. Where the chimeric poxvirus comprises a transgene, the nucleic acid of the chimeric poxvirus comprises an anticancer nucleic acid sequence, a nucleic acid binding sequence, a nucleic acid sequence encoding a detectable moiety, or any combination thereof. Thus, in one aspect is a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, wherein the nucleic acid sequence is (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit Vaccinia virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Radle-Pantylum, vaccinia virus strain AS, sheeppox virus strain NZ2 and nucleic acid fragments from two or more poxvirus strains selected from the group consisting of pseudo vaccinia virus strain TJS; (ii) one or more anticancer nucleic acid sequences; or (iii) a detectable moiety encoding nucleic acid sequence.

In one embodiment, a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence is (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbitpox virus strain Utrecht, vacci nucleic acid fragments from vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Elora, and vaccinia virus strain AS; (ii) one or more anticancer nucleic acid sequences; or (iii) a detectable moiety encoding nucleic acid sequence.

In one aspect is a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises (i) nucleic acid fragments from sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS; (ii) one or more anticancer nucleic acid sequences; or (iii) a detectable moiety encoding nucleic acid sequence.

In one embodiment is a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 3, wherein the nucleic acid sequence is (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbitpox virus strain Utrecht, vacci nucleic acid fragments from vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Elora, and vaccinia virus strain AS; (ii) one or more anticancer nucleic acid sequences; or (iii) a detectable moiety encoding nucleic acid sequence.

As used herein, the term "anti-cancer nucleic acid sequence" or "anti-cancer nucleic acid sequences" refers to a chimeric poxvirus provided herein that has anti-neoplastic properties, and/or inhibits the growth or proliferation of cancer cells and/or in cancer cells compared to healthy cells ( refers to a nucleic acid sequence that has the ability to provide selective expression of (including embodiments thereof). Anti-cancer nucleic acid sequences can inhibit or temporarily or permanently delay the progression of cancer. Examples of anti-cancer nucleic acid sequences include sequences encoding proteins whose expression directly or indirectly inhibits cancer cell growth. For example, an anti-cancer nucleic acid sequence provided herein may encode a protein (eg, the sodium iodide transporter) that is expressed at higher levels in cancer cells compared to healthy cells. In another non-limiting example, the anti-cancer nucleic acid sequence may encode a polypeptide (antibody) capable of de-repressing an anti-tumor immune response (eg, an anti-PD-L1 antibody or fragment thereof). can In an embodiment, the anti-cancer nucleic acid sequence comprises a nucleic acid sequence capable of increasing expression/replication of the chimeric poxvirus in cancer cells compared to healthy cells. Thus, in an embodiment, the rate of expression (eg, transcription, translation) of a chimeric poxvirus comprising an anti-cancer nucleic acid sequence is reduced in healthy cells compared to cancer cells. In an embodiment, a chimeric poxvirus comprising an anti-cancer nucleic acid sequence is not expressed in detectable amounts in healthy cells. In an embodiment, the anticancer nucleic acid sequence is a nucleic acid binding sequence. In an embodiment, the anti-cancer nucleic acid sequence comprises a nucleic acid binding sequence.

As used herein, "nucleic acid binding sequence" refers to a nucleic acid sequence capable of binding (hybridizing) to at least partially complementary cellular nucleic acids (e.g., DNA, RNA, miRNA), which cellular nucleic acids are healthy compared to cancer cells. It is present in increased amounts in cells. A nucleic acid binding sequence provided herein may form part of a nucleic acid comprised in a chimeric poxvirus and may be operably linked to a gene of the chimeric poxvirus. Upon binding of the nucleic acid binding sequence to the cellular nucleic acid, the chimeric poxvirus gene may be targeted for degradation (hydrolysis), reducing expression/replication of the chimeric poxvirus. In an embodiment, the nucleic acid binding sequence is a DNA binding sequence. In an embodiment, the nucleic acid binding sequence is an RNA binding sequence. In an embodiment, the nucleic acid binding sequence is a miRNA binding sequence. Thus, in an embodiment, the anticancer nucleic acid sequence is a nucleic acid binding sequence. In an embodiment, the anti-cancer nucleic acid sequence is a DNA binding sequence. In an embodiment, the anti-cancer nucleic acid sequence is an RNA binding sequence. In an embodiment, the anti-cancer nucleic acid sequence is a miRNA binding sequence.

As used herein, “a nucleic acid sequence encoding a detectable moiety” refers to a nucleic acid sequence encoding a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, chemical or other physical means. A nucleic acid sequence encoding a detectable moiety may encode a fluorescent moiety. Non-limiting examples of fluorescent moieties are mcherry, emerald and firefly luciferase.

In one embodiment is a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, wherein the nucleic acid sequence is (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia virus strain Radle-Pantyno, vaccinia virus strain AS, sheeppox virus strain NZ2 and pseudo nucleic acid fragments from two or more poxvirus strains selected from the group consisting of vaccinia virus strain TJS; (ii) one or more anticancer nucleic acid sequences; (iii) one or more nucleic acid binding sequences; or (iv) a detectable moiety encoding nucleic acid sequence.

In another embodiment is a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, nucleic acid fragments from vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Radle-Elora, and vaccinia virus strain AS; (ii) one or more anticancer nucleic acid sequences; (iii) one or more nucleic acid binding sequences; or (iv) a detectable moiety encoding nucleic acid sequence.

In another embodiment is a chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises (i) nucleic acid fragments from pox virus strain NZ2 and pseudo vaccinia virus strain TJS; (ii) one or more anticancer nucleic acid sequences; (iii) one or more nucleic acid binding sequences; or (iv) a detectable moiety encoding nucleic acid sequence.

in another aspect A chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 3, wherein the nucleic acid sequence comprises (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, nucleic acid fragments from vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ladle-Panoma, and vaccinia virus strain AS; (ii) one or more anticancer nucleic acid sequences; (iii) one or more nucleic acid binding sequences; or (iv) a detectable moiety encoding nucleic acid sequence.

In an embodiment, the nucleic acid sequence comprises (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, nucleic acid fragments from two or more poxvirus strains selected from the group comprising vaccinia virus strain Ledle-Pyanodiac, vaccinia virus strain AS, sheeppox virus strain NZ2, and pseudopox virus strain TJS; and (ii) one or more anti-cancer nucleic acid sequences. In an embodiment, the nucleic acid fragments are vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbitpox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia It is derived from the nia virus strain Ledle-Pyanobacteria and the vaccinia virus strain AS. In an embodiment, the nucleic acid fragment is from vaccinia virus strain NZ2 and pseudo vaccinia virus strain TJS.

In an embodiment, the nucleic acid sequence comprises (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, nucleic acid fragments from two or more poxvirus strains selected from the group consisting of vaccinia virus strain Ledle-Panoma, vaccinia virus strain AS, sheeppox virus strain NZ2, and pseudopox virus strain TJS; and (ii) one or more nucleic acid binding sequences. In an embodiment, the nucleic acid fragments are vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbitpox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia It is derived from the nia virus strain Ledle-Pyanobacteria and the vaccinia virus strain AS. In an embodiment, the nucleic acid fragment is from vaccinia virus strain NZ2 and pseudo vaccinia virus strain TJS.

In an embodiment, the nucleic acid sequence comprises (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, nucleic acid fragments from two or more poxvirus strains selected from the group consisting of vaccinia virus strain Ledle-Panoma, vaccinia virus strain AS, sheeppox virus strain NZ2, and pseudopox virus strain TJS; and (ii) a nucleic acid sequence encoding a detectable moiety. In an embodiment, the nucleic acid fragments are vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbitpox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia It is derived from the nia virus strain Ledle-Pyanobacteria and the vaccinia virus strain AS. In an embodiment, the nucleic acid fragment is from vaccinia virus strain NZ2 and pseudo vaccinia virus strain TJS.

In an embodiment, the nucleic acid sequence comprises (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, nucleic acid fragments from two or more poxvirus strains selected from the group consisting of vaccinia virus strain Ledle-Panoma, vaccinia virus strain AS, sheeppox virus strain NZ2, and pseudopox virus strain TJS; (ii) one or more anticancer nucleic acid sequences; and (iii) a nucleic acid sequence encoding a detectable moiety. In an embodiment, the nucleic acid fragments are vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbitpox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia It is derived from the nia virus strain Ledle-Pyanobacteria and the vaccinia virus strain AS. In an embodiment, the nucleic acid fragment is from vaccinia virus strain NZ2 and pseudo vaccinia virus strain TJS.

In an embodiment, the nucleic acid sequence comprises (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, nucleic acid fragments from two or more poxvirus strains selected from the group consisting of vaccinia virus strain Ledle-Panoma, vaccinia virus strain AS, sheeppox virus strain NZ2, and pseudopox virus strain TJS; (ii) one or more anticancer nucleic acid sequences; and (iii) one or more nucleic acid binding sequences. In an embodiment, the nucleic acid fragments are vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbitpox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia It is derived from the nia virus strain Ledle-Pyanobacteria and the vaccinia virus strain AS. In an embodiment, the nucleic acid fragment is from vaccinia virus strain NZ2 and pseudo vaccinia virus strain TJS.

Anti-cancer nucleic acid sequences (transgenes), including embodiments thereof, may form part of the genome of a chimeric poxvirus provided herein. The chimeric poxvirus genome contains genes necessary for poxvirus expression and replication. Genes required for chimeric poxvirus expression and replication are referred to herein as “essential genes”. Genes that are not required for the expression and replication of the chimeric poxvirus are referred to herein as “non-essential genes”. The anti-cancer nucleic acid sequence can be integrated into the chimeric poxvirus genome through intragenic insertion or operably linked to the gene. When inserting an anti-cancer nucleic acid sequence into a chimeric poxvirus gene, a gene (eg, a non-essential gene) or part thereof may be deleted. In an embodiment, the one or more anti-cancer nucleic acid sequences form part of a non-essential gene of the chimeric poxvirus. In an embodiment, one or more anti-cancer nucleic acid sequences are inserted into non-essential genes of the chimeric poxvirus. In an embodiment, the non-essential gene is a thymidine kinase gene. In an embodiment, the non-essential gene is the J2R gene. In an embodiment, the non-essential gene is the F14.5L gene.

As discussed above, anti-cancer nucleic acid sequences can encode polypeptides useful for the treatment of cancer. In an embodiment, the one or more anti-cancer nucleic acid sequences independently encode a PD-L1 inhibitor or sodium iodine cotransporter. In an embodiment, the PD-L1 inhibitor is an anti-PD-L1 scFv. In an embodiment, the anti-PD-L1 scFv comprises the sequence of SEQ ID NO: 17. In an embodiment, the anti-PD-L1 scFv is the sequence of SEQ ID NO: 17. In an embodiment, the sodium iodine cotransporter comprises the sequence of SEQ ID NO: 13. In an embodiment, the sodium iodine cotransporter is the sequence SEQ ID NO:13.

As referred to herein, "PD-L1" or "PD-L1 protein" is any recombinant or naturally occurring form of programmed death ligand 1 (PD-L1), also known as cluster of differentiation 274 (CD 274). or a variant or homolog thereof that retains (within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% compared to PD-L1) PD-L1 activity. include In some embodiments, a variant or homologue has an entire sequence or a portion of a sequence (eg, a portion of 50, 100, 200, 100, 150 or 200 contiguous amino acids) compared to a naturally occurring PD-L1 protein. In an embodiment, the PD-L1 protein is substantially identical to, or a variant or homolog with substantial identity to, the protein identified by UniProt reference number Q9NZQ7.

As provided herein, the term “PD-L1 inhibitor” refers to a substance (e.g., an antibody, antibody fragment, single chain variable fragment [scFv]) capable of detectably lowering the level of expression or activity of PD-L1 compared to a control. refers to The suppressed expression or activity of PD-L1 may be no greater than 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% relative to a control. In some cases, the inhibition is 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold or more relative to the control. A PD-L1 inhibitor, for example, at least partially or completely blocks stimulation of PD-L1, reduces, prevents or delays activation of PD-L1, or inactivates PD-L1, compared to the absence of the PD-L1 inhibitor. inhibits PD-L1 by desensitizing, downregulating, or downregulating the signaling, activity or amount of PD-L1.

The term "sodium iodine cotransporter", "NIS" or "hNIS" as referred to herein refers to the activity of any recombinant or naturally occurring form of sodium iodine cotransporter or sodium iodine cotransporter (as compared to sodium iodine cotransporter by at least 50%). %, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some embodiments, the variant or homolog is at least 90% over an entire sequence or a portion of a sequence (e.g., a portion of 50, 100, 200, 100, 150 or 200 contiguous amino acids) compared to a naturally occurring sodium iodine cotransporter. , 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity. In an embodiment, the sodium iodine cotransporter is substantially identical to, or a variant or homolog with substantial identity to, the protein identified by Uniprot reference number Q92911. In an embodiment, the sodium iodine cotransporter comprises the sequence of SEQ ID NO: 13. In an embodiment, the sodium iodine cotransporter is the sequence SEQ ID NO:13.

Expression of the anti-cancer nucleic acid sequences provided herein may be regulated by a promoter. Thus, in an embodiment, one or more anti-cancer nucleic acid sequences are each operably linked to a promoter. In an embodiment, the promoter is a vaccinia virus early promoter. In an embodiment, the promoter is a synthetic early promoter. In an embodiment, the synthetic early promoter comprises the sequence of SEQ ID NO: 19. In an embodiment, the synthetic early promoter is the sequence of SEQ ID NO: 19. In an embodiment, the promoter is a vaccinia virus late promoter. In an embodiment, the promoter is the H5 promoter or the 11K promoter. In an embodiment, the H5 promoter comprises the sequence of SEQ ID NO: 18. In an embodiment, the H5 promoter is the sequence of SEQ ID NO: 18. In an embodiment, the 11K promoter comprises the sequence of SEQ ID NO:20. In an embodiment, the 11K promoter is the sequence of SEQ ID NO:20.

Anti-cancer nucleic acid sequences (nucleic acid binding sequences) provided herein can be integrated into a chimeric poxvirus genome to be placed in a functional relationship (operably linked) with a particular poxvirus gene. For example, an anti-cancer nucleic acid sequence (nucleic acid binding sequence) can be operably linked to a poxvirus gene if it affects transcription or translation of the poxvirus gene. Generally, the anti-cancer nucleic acid sequence (nucleic acid binding sequence) and the poxvirus gene are operably linked when contiguous and/or when in read state. In an embodiment, one or more anticancer nucleic acid sequences (one or more nucleic acid binding sequences) are operably linked to essential genes of the chimeric poxvirus. In an embodiment, the one or more anticancer nucleic acid sequences (one or more nucleic acid binding sequences) are operably linked to the DNA polymerase gene of the chimeric poxvirus. In an embodiment, one or more anti-cancer nucleic acid sequences (one or more nucleic acid binding sequences) are operably linked to the 3' end of the DNA polymerase gene of the chimeric poxvirus. In an embodiment, one or more anticancer nucleic acid sequences (one or more nucleic acid binding sequences) are operably linked to a uracil DNA glycosylase gene. In an embodiment, one or more anticancer nucleic acid sequences (one or more nucleic acid binding sequences) are operably linked to the 3' end of the uracil DNA glycosylase gene.

In an embodiment, the one or more anticancer nucleic acid sequences (one or more nucleic acid binding sequences) independently encode a miRNA binding sequence. In an embodiment, the miRNA binding sequence is a miR100 binding sequence or a let7c binding sequence. In an embodiment, the miRNA binding sequence is a miR100 binding sequence. In an embodiment, the miR100 binding sequence comprises the sequence of SEQ ID NO:9. In an embodiment, the miR100 binding sequence is the sequence of SEQ ID NO:9. In an embodiment, the miR100 binding sequence comprises the sequence of SEQ ID NO: 10. In an embodiment, the miR100 binding sequence is the sequence of SEQ ID NO:10. In an embodiment, the miRNA binding sequence is a let7c binding sequence. In an embodiment, the let7c binding sequence comprises the sequence of SEQ ID NO: 11. In an embodiment, the let7c binding sequence is the sequence of SEQ ID NO: 11.

In an embodiment, the one or more anti-cancer nucleic acid sequences are a first anti-cancer nucleic acid sequence and a second anti-cancer nucleic acid sequence. As provided herein, the first anti-cancer nucleic acid sequence can be a first nucleic acid-binding sequence and the second anti-cancer nucleic acid sequence can be a second nucleic acid-binding sequence.

In an embodiment, the first anti-cancer nucleic acid sequence encodes a sodium iodine cotransporter and the second anti-cancer nucleic acid sequence (second nucleic acid binding sequence) encodes a miRNA binding sequence. In an embodiment, a first anti-cancer nucleic acid sequence forms part of a thymidine kinase gene and a second anti-cancer nucleic acid sequence (second nucleic acid binding sequence) is operably linked to a uracil DNA glycosylase gene. In an embodiment, a first anti-cancer nucleic acid sequence forms part of a thymidine kinase gene and a second anti-cancer nucleic acid sequence (second nucleic acid binding sequence) is operably linked to a DNA polymerase gene.

In an embodiment, the first anti-cancer nucleic acid sequence encodes a sodium iodine cotransporter and the second anti-cancer nucleic acid sequence encodes a PD-L1 inhibitor. In an embodiment, the first anti-cancer nucleic acid sequence forms part of a thymidine kinase gene and the second anti-cancer nucleic acid sequence forms part of a F14.5L gene.

In an embodiment, the nucleic acid sequence comprises (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, nucleic acid fragments from two or more poxvirus strains selected from the group consisting of vaccinia virus strain Ledle-Panoma, vaccinia virus strain AS, sheeppox virus strain NZ2, and pseudopox virus strain TJS; and (ii) a nucleic acid sequence encoding the detectable moiety. In an embodiment, the detectable moiety encoding nucleic acid sequence encodes a fluorescent moiety. In an embodiment, the detectable moiety encoding nucleic acid sequence forms part of a nonessential gene of the chimeric poxvirus. In an embodiment, the non-essential gene is a thymidine kinase gene. In an embodiment, a portion of a nonessential gene is deleted.

In an embodiment, a nucleic acid sequence encoding a detectable moiety is operably linked to a promoter. In an embodiment, the promoter is a vaccinia virus early promoter. In an embodiment, the promoter is a synthetic early promoter. In an embodiment, the synthetic early promoter comprises the sequence of SEQ ID NO: 19. In an embodiment, the synthetic early promoter is the sequence of SEQ ID NO: 19. In an embodiment, the promoter is a vaccinia virus late promoter. In an embodiment, the promoter is the H5 promoter or the 11K promoter. In an embodiment, the H5 promoter comprises the sequence of SEQ ID NO: 18. In an embodiment, the H5 promoter is the sequence of SEQ ID NO: 18. In an embodiment, the 11K promoter comprises the sequence of SEQ ID NO:20. In an embodiment, the 11K promoter is the sequence of SEQ ID NO:20.

In one embodiment, the anti-cancer nucleic acid sequence (nucleic acid binding sequence) encodes a miRNA binding sequence having the sequence of SEQ ID NO: 10 and is operably linked to the 3' end of the uracil DNA glycosylase gene.

In one embodiment, the anticancer nucleic acid sequence (nucleic acid binding sequence) encodes a miRNA binding sequence having the sequence of SEQ ID NO: 9 and is operably linked to the 3' end of the uracil DNA glycosylase gene.

In one embodiment, the anti-cancer nucleic acid sequence (nucleic acid binding sequence) encodes a miRNA binding sequence having the sequence of SEQ ID NO: 11 and is operably linked to the 3' end of the uracil DNA glycosylase gene.

In one embodiment, the anti-cancer nucleic acid sequence (nucleic acid binding sequence) encodes a miRNA binding sequence having the sequence of SEQ ID NO: 9 and is operably linked to the 3' end of the DNA polymerase gene.

In one embodiment, the anticancer nucleic acid sequence (nucleic acid binding sequence) encodes a miRNA binding sequence having the sequence of SEQ ID NO: 11 and is operably linked to the 3' end of the DNA polymerase gene.

In one embodiment, the thymidine kinase gene of the chimeric poxvirus has the sequence of SEQ ID NO:5.

In one embodiment, the anti-cancer nucleic acid sequence encodes a sodium iodine cotransporter, is operably linked to a synthetic early promoter, and forms part of a thymidine kinase gene, wherein the sodium iodine cotransporter has SEQ ID NO: 13 and is synthesized The early promoter has the sequence of SEQ ID NO: 19.

In one embodiment, the detectable moiety encoding nucleic acid sequence encodes a fluorescent moiety having the sequence of SEQ ID NO: 14, operably linked to an H5 promoter, and forms part of a thymidine kinase gene, wherein the H5 promoter comprises: It has the sequence of SEQ ID NO: 18.

In one embodiment, the detectable moiety encoding nucleic acid sequence encodes a fluorescent moiety having the sequence of SEQ ID NO: 15, operably linked to a synthetic incipient promoter, and forms part of a thymidine kinase gene, The promoter has the sequence of SEQ ID NO: 19.

In one embodiment, the detectable moiety encoding nucleic acid sequence encodes a fluorescent moiety having the sequence of SEQ ID NO: 15, operably linked to an H5 promoter, and forms part of a thymidine kinase gene, wherein the H5 promoter comprises: It has the sequence of SEQ ID NO: 18.

In one embodiment, the detectable moiety encoding nucleic acid sequence encodes a fluorescent moiety having the sequence of SEQ ID NO: 15, operably linked to an 11K promoter, and forms part of a thymidine kinase gene, wherein the 11K promoter comprises: It has the sequence of SEQ ID NO: 20.

In one embodiment, the detectable moiety encoding nucleic acid sequence encodes a fluorescent moiety having the sequence of SEQ ID NO: 16, operably linked to an H5 promoter, and forming part of a thymidine kinase gene, wherein the H5 promoter comprises: It has the sequence of SEQ ID NO: 18.

In one embodiment, the detectable moiety encoding nucleic acid sequence encodes a fluorescent moiety having the sequence of SEQ ID NO: 16 and is operably linked to an 11K promoter and forms part of a thymidine kinase gene, wherein said 11K promoter SEQ ID NO: It has a sequence of 20.

In one embodiment, the first anticancer nucleic acid sequence encodes a sodium iodine cotransporter, is operably linked to a synthetic early promoter, and forms part of a thymidine kinase gene; The second anti-cancer nucleic acid sequence (nucleic acid binding sequence) encodes a miRNA binding sequence having the sequence of SEQ ID NO: 10, operably linked to the 3' end of the uracil DNA glycosylase gene, and the sodium iodine cotransporter is SEQ ID NO: 13, and the synthetic early promoter has the sequence of SEQ ID NO: 19.

In one embodiment, the first anticancer nucleic acid sequence encodes a sodium iodine cotransporter, is operably linked to a synthetic early promoter, and forms part of a thymidine kinase gene; The second anticancer nucleic acid sequence (nucleic acid binding sequence) encodes a miRNA binding sequence having the sequence of SEQ ID NO: 9, operably linked to the 3' end of the uracil DNA glycosylase gene, and the sodium iodine cotransporter is SEQ ID NO: 13, and the synthetic early promoter has the sequence of SEQ ID NO: 19.

In one embodiment, the first anticancer nucleic acid sequence encodes a sodium iodine cotransporter, is operably linked to a synthetic early promoter, and forms part of a thymidine kinase gene; The second anticancer nucleic acid sequence (nucleic acid binding sequence) encodes a miRNA binding sequence having the sequence of SEQ ID NO: 11, operably linked to the 3' end of the uracil DNA glycosylase gene, and the sodium iodine cotransporter is SEQ ID NO: 13, and the synthetic early promoter has the sequence of SEQ ID NO: 19.

In one embodiment, the first anticancer nucleic acid sequence encodes a sodium iodine cotransporter, is operably linked to a synthetic early promoter, and forms part of a thymidine kinase gene; The second anticancer nucleic acid sequence (nucleic acid binding sequence) encodes a miRNA binding sequence having the sequence of SEQ ID NO: 9, operably linked to the 3' end of the DNA polymerase gene, and the sodium iodine cotransporter of SEQ ID NO: 13 and the synthetic initial promoter has the sequence of SEQ ID NO: 19.

In one embodiment, the first anticancer nucleic acid sequence encodes a sodium iodine cotransporter, is operably linked to a synthetic early promoter, and forms part of a thymidine kinase gene; The second anti-cancer nucleic acid sequence (nucleic acid binding sequence) encodes a miRNA binding sequence having the sequence of SEQ ID NO: 11, operably linked to the 3' end of the DNA polymerase gene, and the sodium iodine cotransporter of SEQ ID NO: 13 and the synthetic initial promoter has the sequence of SEQ ID NO: 19.

In one embodiment, the F14.5L gene of the chimeric poxvirus has the sequence of SEQ ID NO: 7

In one embodiment, the anti-cancer nucleic acid sequence encodes an anti-PD-L1 scFv, is operably linked to an H5 promoter, and forms part of the F14.5L gene, said anti-PD-L1 scFv comprising the sequence of SEQ ID NO: 17 And the H5 promoter has the sequence of SEQ ID NO: 18.

In one embodiment, the anti-cancer nucleic acid sequence encodes a sodium iodine cotransporter, is operably linked to a synthetic early promoter, forms part of a thymidine kinase gene, and the F14.5L gene has the sequence of SEQ ID NO: 7, wherein The sodium iodine cotransporter has the sequence of SEQ ID NO: 13, and the synthetic early promoter has the sequence of SEQ ID NO: 19.

In one embodiment, the first anticancer nucleic acid sequence encodes a sodium iodine cotransporter, is operably linked to a synthetic early promoter, and forms part of a thymidine kinase gene; The second anti-cancer nucleic acid sequence encodes an anti-PD-L1 scFv, is operably linked to the H5 promoter, forms part of the F14.5L gene, the sodium iodine cotransporter has the sequence of SEQ ID NO: 13, and is synthesized The early promoter has the sequence SEQ ID NO: 19, the anti-PD-L1 scFv has the sequence SEQ ID NO: 17, and the H5 promoter has the sequence SEQ ID NO: 18.

IV. chimera How to form a poxvirus

In another embodiment, a method for forming a chimeric poxvirus is provided, comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia Infecting a cell with two or more poxvirus strains selected from the group consisting of vaccinia virus strain CL, vaccinia virus strain Ledle-Yoranella, vaccinia virus strain AS, sheeppox virus strain NZ2 and pseudovax virus strain TJS; and allowing two or more poxvirus strains to replicate to form a chimeric poxvirus.

The methods for forming chimeric poxviruses provided herein can be used to form chimeric poxviruses comprising the transgenes described herein (eg, anti-cancer nucleic acid sequences, nucleic acid binding sequences, nucleic acid sequences encoding detectable moieties). .

In an embodiment, two or more poxvirus strains are each present at a multiplicity of infection of less than about 1.0. In an embodiment, two or more poxvirus strains are each present at a multiplicity of infection of less than about 0.5. In an embodiment, two or more poxvirus strains are each present at a multiplicity of infection of less than about 0.1. In an embodiment, two or more poxvirus strains are each present at a multiplicity of infection of less than about 0.05. In an embodiment, two or more poxvirus strains are each present at a multiplicity of infection of less than about 0.01.

In an embodiment, the chimeric poxvirus is vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbitpox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, Infecting the cells with two or more poxvirus strains selected from the group comprising vaccinia virus strain Ledle-Panthox, vaccinia virus strain AS, sheeppox virus strain NZ2 and pseudovax virus strain TJS; It is formed by a method comprising allowing two or more poxvirus strains to replicate to form a chimeric poxvirus.

In an embodiment, the cell is vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbitpox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia Infected with the virus strain Radle-Illinois and the vaccinia virus strain AS.

In an embodiment, the nucleic acid fragments are vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbitpox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia It is derived from the nia virus strain Ledle-Pyanobacteria and the vaccinia virus strain AS.

In an embodiment, the cells are infected with vaccinia virus strain Brighton and raccoon fox virus strain Herman. In an embodiment, the cells are infected with vaccinia virus strain Brighton and rabbitpox virus strain Utrecht. In an embodiment, the cells are infected with vaccinia virus strain Brighton and vaccinia virus strain WR. In an embodiment, the cells are infected with vaccinia virus strain Brighton and vaccinia virus strain IHD. In an embodiment, the cells are infected with vaccinia virus strain Brighton and vaccinia virus strain Elstree. In an embodiment, the cells are infected with vaccinia virus strain Brighton and vaccinia virus strain CL. In an embodiment, the cells are infected with vaccinia virus strain Brighton and vaccinia virus strain Ledle-Eliotella. In an embodiment, the cells are infected with vaccinia virus strain Brighton and vaccinia virus strain AS. In an embodiment, the cells are infected with vaccinia virus strain Brighton and sheeppox virus strain NZ2. In an embodiment, the cells are infected with vaccinia virus strain Brighton and pseudovax virus strain TJS.

In an embodiment, the cells are infected with pox rabbit virus strain Utrecht and vaccinia virus strain WR. In an embodiment, the cells are infected with pox rabbit virus strain Utrecht and vaccinia virus strain IHD. In an embodiment, the cells are infected with rabbitpox virus strain Utrecht and vaccinia virus strain Elstri. In an embodiment, the cells are infected with pox rabbit virus strain Utrecht and vaccinia virus strain CL. In an embodiment, the cells are infected with rabbitpox virus strain Utrecht and vaccinia virus strain Ledle-Panto. In an embodiment, the cells are infected with pox rabbit virus strain Utrecht and vaccinia virus strain AS. In an embodiment, the cells are infected with pox rabbit virus strain Utrecht and sheeppox virus strain NZ2. In an embodiment, the cells are infected with rabbitpox virus strain Utrecht and pseudovax virus strain TJS.

In an embodiment, the cells are infected with vaccinia virus strain WR and vaccinia virus strain IHD. In an embodiment, the cells are infected with vaccinia virus strain WR and vaccinia virus strain Elstri. In an embodiment, the cells are infected with vaccinia virus strain WR and vaccinia virus strain CL. In an embodiment, the cells are infected with vaccinia virus strain WR and vaccinia virus strain Ledle-Pylum. In an embodiment, the cells are infected with vaccinia virus strain WR and vaccinia virus strain AS. In an embodiment, the cells are infected with vaccinia virus strain WR and sheeppox virus strain NZ2. In an embodiment, the cells are infected with vaccinia virus strain WR and pseudovax virus strain TJS.

In an embodiment, the cells are infected with vaccinia virus strain IHD and vaccinia virus strain Elstri. In an embodiment, the cells are infected with vaccinia virus strain IHD and vaccinia virus strain CL. In an embodiment, the cells are infected with vaccinia virus strain IHD and vaccinia virus strain Ledle-Illanoma. In an embodiment, the cells are infected with vaccinia virus strain IHD and vaccinia virus strain AS. In an embodiment, the cells are infected with vaccinia virus strain IHD and sheeppox virus strain NZ2. In an embodiment, the cells are infected with vaccinia virus strain IHD and pseudovax virus strain TJS.

In an embodiment, the cells are infected with vaccinia virus strain Elstri and vaccinia virus strain CL. In an embodiment, the cells are infected with vaccinia virus strain Elstri and vaccinia virus strain Ledle-Plan. In an embodiment, the cells are infected with vaccinia virus strain Elstri and vaccinia virus strain AS. In an embodiment, the cells are infected with vaccinia virus strain Elstri and sheeppox virus strain NZ2. In an embodiment, the cells are infected with vaccinia virus strain Elstri and pseudovax virus strain TJS.

In an embodiment, the cells are infected with vaccinia virus strain CL and vaccinia virus strain Ledle-Panto. In an embodiment, the cells are infected with vaccinia virus strain CL and vaccinia virus strain AS. In an embodiment, the cells are infected with vaccinia virus strain CL and sheeppox virus strain NZ2. In an embodiment, the cells are infected with vaccinia virus strain CL and pseudovax virus strain TJS.

In an embodiment, the cells are infected with vaccinia virus strain Ledle-Allantoic and vaccinia virus strain AS. In an embodiment, the cells are infected with vaccinia virus strain Ledle-Allantoic and sheeppox virus strain NZ2. In an embodiment, the cells are infected with vaccinia virus strain Ledle-ileotype and pseudovax virus strain TJS.

In an embodiment, the cells are infected with vaccinia virus strain AS and sheeppox virus strain NZ2. In an embodiment, the cells are infected with vaccinia virus strain AS and pseudovax virus strain TJS. In an embodiment, the cells are infected with vaccinia virus strain NZ2 and pseudo vaccinia virus strain TJS.

In an embodiment, the cell is a renal fibroblast. Cells are epithelial cells. In an embodiment, the cell is a CV-1 cell. In an embodiment, the cell is a bovine renal epithelial cell.

V. Pharmaceutical Compositions

In one aspect, a pharmaceutical composition comprising a therapeutically effective amount of a chimeric poxvirus (including embodiments thereof) described herein is provided. In embodiments, the chimeric poxvirus comprises a transgene (eg, an anti-cancer nucleic acid sequence, a nucleic acid binding sequence, a nucleic acid sequence encoding a detectable moiety, or any combination thereof).

"Pharmaceutically acceptable excipient" and "pharmaceutically acceptable carrier" refer to a substance that aids administration of an active agent and absorption by a subject, and can be included in the composition of the present invention without causing serious toxicological side effects to the patient. can Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, physiological saline, Lactated Ringer's solution, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coating agents, sweeteners, flavoring agents, salt solutions (e.g. , Ringer's solution), alcohol, oil, gelatin, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidine, and pigments. The formulation may be sterilized and, if desired, may contain adjuvants such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts that affect osmotic pressure, buffers, colorants and/or fragrances that do not cause harmful reactions with the compounds of the present invention. can be mixed. One skilled in the art will recognize that other pharmaceutical excipients are useful in the present invention.

Chimeric poxvirus compositions (including embodiments thereof) provided herein may be administered orally, gastrointestinally, or rectally. Administration can be in the form of a single bolus administration or can be by, for example, a continuous perfusion pump. In an embodiment, a chimeric poxvirus provided herein is combined with one or more excipients such as disintegrants, fillers, lubricants or preservatives. In an embodiment, a chimeric poxvirus provided herein forms part of a capsule. Suitable capsules include both hard shell capsules and soft shell capsules. Any lipid based or polymer based colloid can be used to form the capsule. Exemplary polymers useful in colloidal formulations include gelatin, vegetable polysaccharides or derivatives thereof such as carrageenan and starch, and modified forms of cellulose such as hypromellose. If desired, other ingredients may be added to the gelling solution, for example plasticizers such as glycerin and/or sorbitol to reduce the hardness of the capsules, colorants, preservatives, disintegrants, lubricants and surface treatment agents.

The chimeric poxvirus composition may be formulated in unit dosage form, each dosage containing from about 0.005 mg to about 2000 mg of a given chimeric poxvirus having minimal urease activity per administration. The term “dosage unit dosage form” refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each containing a predetermined amount of the active substance calculated to produce the desired therapeutic effect in association with suitable pharmaceutical excipients. means a unit that For preparing solid compositions such as tablets, the principal active ingredient is mixed with a pharmaceutical excipient to form a solid preformulated composition containing a homogeneous mixture of the compound of the present invention. When referring to such preformulated compositions as homogeneous, the active ingredient is typically dispersed evenly throughout the composition so that the composition may be readily subdivided into equally effective unit dosage forms, such as tablets, pills, and capsules.

In some embodiments, tablets or pills of the present invention may be coated or otherwise formulated to provide a dosage form that provides the benefit of prolonged action. For example, a tablet or pill may contain an internal dosage component and an external dosage component, the latter being the form of an envelope for the former dosage component. The two components are resistant to disintegration in the stomach and can be separated by an enteric layer which serves to allow the internal components to pass intact into the duodenum or to delay release. A variety of materials can be used in the enteric layer or coating, including a number of polymeric acids and mixtures of polymeric acids with materials such as shellac, cetyl alcohol and cellulose acetate.

Liquid forms in which the compositions of the present invention may be formulated for administration orally or by injection include elixirs and similar pharmaceutical vehicles, as well as flavored emulsions, including edible oils such as cottonseed oil, sesame oil, coconut oil or peanut oil, aqueous solutions. or oil suspensions, suitably flavored syrups and aqueous solutions.

VI. treatment method

In another aspect is a method of treating cancer in a subject in need thereof, comprising the step of treating cancer in a subject by administering to the subject a therapeutically effective amount of a chimeric poxvirus described herein, including embodiments thereof. A method is provided. In an embodiment, the cancer is breast cancer, colon cancer, kidney cancer, leukemia, lung cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer, brain cancer, liver cancer, stomach cancer, or sarcoma. In an embodiment, the cancer is breast cancer. In an embodiment, the cancer is colorectal cancer. In an embodiment, the cancer is renal cancer. In an embodiment, the cancer is leukemia. In an embodiment, the cancer is lung cancer. In an embodiment, the cancer is melanoma. In an embodiment, the cancer is ovarian cancer. In an embodiment, the cancer is prostate cancer. In an embodiment, the cancer is pancreatic cancer. In an embodiment, the cancer is brain cancer. In an embodiment, the cancer is liver cancer. In an embodiment, the cancer is gastric cancer. In an embodiment, the cancer is a sarcoma. In an embodiment, the cancer is triple negative breast cancer.

In embodiments, administering comprises administering a first chimeric poxvirus and a second chimeric poxvirus. In an embodiment, the first chimeric poxvirus and the second chimeric poxvirus are administered in synergistic amounts in combination. In an embodiment, the first chimeric poxvirus and the second chimeric poxvirus are administered simultaneously. In an embodiment, the first chimeric poxvirus and the second chimeric poxvirus are administered sequentially.

In an embodiment, the poxvirus is administered at at least 10 ³ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at at least 10 ⁴ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at at least 10 ⁵ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at at least 10 ⁶ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at at least 10 ⁷ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at at least 10 ⁸ plaque forming units (Pfu)/kg.

In an embodiment, the poxvirus is administered at 10 ³ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at 10 ⁴ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at 10 ⁵ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at 10 ⁶ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at 10 ⁷ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at 10 ⁸ plaque forming units (Pfu)/kg.

In an embodiment, the poxvirus is administered at about 10 ³ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at 10 ³ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at about 4×10 ⁴ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at 4×10 ⁴ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at about 5x10 ⁴ plaque forming units (Pfu)/kg. In an embodiment, the poxvirus is administered at 5×10 ⁴ plaque forming units (Pfu)/kg.

In one aspect, a method of inhibiting cell proliferation of a cell is provided, comprising contacting the cell with a chimeric poxvirus described herein. In an embodiment, the cell is a cancer cell. Cancer cells are breast cancer cells, colon cancer cells, renal cancer cells, leukemia cells, lung cancer cells, melanoma cells, ovarian cancer cells, prostate cancer cells, pancreatic cancer cells, brain cancer cells, liver cancer cells, gastric cancer cells or sarcoma cells. In an embodiment, the cancer cell is a breast cancer cell. In an embodiment, the cancer cell is a colon cancer cell. In an embodiment, the cancer cells are renal cancer cells. In an embodiment, the cancer cell is a leukemia cell. In an embodiment, the cancer cells are lung cancer cells. In an embodiment, the cancer cells are melanoma. In an embodiment, the cancer cells are ovarian cancer cells. In an embodiment, the cancer cells are prostate cancer cells. In an embodiment, the cancer cell is a pancreatic cancer cell. In an embodiment, the cancer cells are brain cancer cells. In an embodiment, the cancer cells are liver cancer cells. In an embodiment, the cancer cells are gastric cancer cells. In an embodiment, the cancer cells are sarcoma cells. In an embodiment, the cancer cells are triple negative breast cancer cells.

According to the methods provided herein, an effective amount of one or more agents provided herein is administered to a subject. The terms effective amount and effective dosage are used interchangeably. The term effective amount is defined as any amount necessary to produce a desired physiological response (eg, cancer treatment). Effective amounts and schedules for administering the agents can be determined empirically by one skilled in the art. The dosage range for administration is a range large enough to produce the desired effect in which one or more symptoms of the disease or disorder are affected (eg, reduced or delayed). The dosage should not be so large as to cause substantial side effects such as unwanted cross-reactions, anaphylactic reactions, and the like. In general, dosages will vary according to age, condition, sex, type of disease, severity of disease or disorder, route of administration, or whether other drugs are included in the regimen, and can be determined by those skilled in the art. Dosage may be adjusted by an individual physician in case of contraindications. The dosage can vary and can be administered in one or more doses administered daily for one or several days. Guidance on dosages appropriate for a given class of medicinal product can be found in the literature. For example, for a given parameter, an effective amount is an increase of at least 5%, 10%, 15%, 20%, 25%, 40%, 50%, 60%, 75%, 80% 90%, or at least 100%. or will show a decrease. Efficacy can also be expressed as a "fold" increase or decrease. For example, a therapeutically effective amount can have an effect of at least 1.2-fold, 1.5-fold, 2-fold, 5-fold or more over a control. The precise dosage and formulation will depend on the therapeutic purpose and will be ascertained by those skilled in the art using known techniques (see, eg, Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Remington: The Science and Practice of Pharmacy, 20th Edition, Gennaro, Editor (2003), and Pickar, Dosage Calculations (1999)).

For prophylactic use, a therapeutically effective amount of a chimeric poxvirus composition described herein is administered to a subject before or during early onset (eg, at early signs and symptoms of cancer). Treatment measures include administering to a subject a therapeutically effective amount of an agent described herein after diagnosis or development of a disease. Accordingly, in another aspect, a method of treating a disease (eg, cancer) in a subject in need thereof is provided.

The terms "subject", "patient", "individual" and the like are not intended to be limiting and are generally interchangeable. That is, an individual described as a “patient” may not necessarily have a particular disease, but may only be seeking medical advice.

As used herein, "treatment" of a condition, disease or disorder, or symptoms associated with a condition, disease or disorder, refers to an approach that results in beneficial or desired results, including clinical results. Beneficial or desired clinical results include alleviation or amelioration of one or more symptoms or conditions, reduction in the severity of a condition, disorder or disease, stabilization of the state of a condition, disorder or disease, prevention of the occurrence of a condition, disorder or disease, condition, disorder or disease prevention of the spread of a disease, delay or delay in the progression of a condition, disorder or disease, delay or delay in the onset of a condition, disorder or disease, amelioration or alleviation of a condition, disorder or disease state, and alleviation, in whole or in part, of the condition, disorder or disease. may, but is not limited thereto. “Treatment” can also mean prolonging the survival of a subject beyond what would be expected in the absence of treatment. "Treatment" can also mean inhibiting the progress of a condition, disorder or disease, temporarily delaying the progress of a condition, disorder or disease, although in some cases, permanently arresting the progress of a condition, disorder or disease. include The terms treatment, treat or treating as used herein refer to a method of reducing the effect of one or more symptoms of a disease or condition characterized by the expression of a protease or a symptom of a disease or condition characterized by the expression of a protease. . Thus, in the disclosed methods, treatment can reduce the severity of an established disease, condition, or symptom of a disease or condition (eg, cancer) by 10%, 20%, 30%, 40%, 50%, 60%, 70% , 80%, 90% or 100% reduction. For example, a method of treating a disease is considered eligible for treatment if a 10% reduction in one or more symptoms of the disease in a subject compared to a control group. Thus, a reduction may be 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% or any reduction between 10% and 100% compared to original or control. can It should be understood that treatment does not necessarily refer to the cure or complete elimination of a disease or condition, or of a disease or condition or symptom. Also, as used herein, reference to reduction, diminution or inhibition refers to a reduction of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or more as compared to control levels. Inclusive of changes, the term may, but need not necessarily include, complete removal.

Regardless of how the chimeric poxvirus composition is formulated, the required dosage depends on the route of administration, the nature of the formulation, the nature of the subject's condition, such as immaturity or gastrointestinal disorders of the immune system, size, weight, surface area, age and sex of the subject. , may vary depending on other medications being administered and the judgment of the attending physician. Alternatively or additionally, the dosage can be expressed as Pfu per kg dry weight.

Administration can be single or multiple (eg, 2-fold or 3-fold, 4-fold, 6-fold, 8-fold, 10-fold, 20-fold, 50-fold, 100-fold, 150-fold or more). The duration of treatment with any of the compositions provided herein can be of any length, from as short as one day to as long as the life of the host (eg, several years). For example, the composition once a week (eg, 4 weeks to several months or years). once a month (eg, for 3 to 12 months or several years); or once a year for a period of 5 years, 10 years or longer. It should also be noted that the frequency of treatment can be variable. For example, the composition can be administered once (or twice, three times, etc.) daily, weekly, monthly or annually.

The composition may also be administered with other therapeutic agents. In embodiments, the composition may be administered with an anti-cancer agent. Other therapeutic agents will depend on the particular disorder, but may include, for example, dietary modification, hemodialysis, therapeutic agents such as sodium benzoate, phenylacetate, arginine, or surgical therapy. Co-administration of two or more therapeutic agents does not require that the agents be administered at the same time or by the same route, as long as there is an overlap in the period during which the agents exert their therapeutic effect. Simultaneous or sequential administration is contemplated, such as administration on different days or different weeks.

Other active agents known to be useful in treating a disease described herein (e.g., breast cancer, colorectal cancer, kidney cancer, leukemia, lung cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer, brain cancer, liver cancer, stomach cancer or sarcoma) For example, anticancer agents), or together with adjuvants that are not effective alone, but may contribute to the efficacy of the active agents, they may be used in combination with each other.

In an embodiment, the method comprises administering a therapeutic agent. In an embodiment, the therapeutic agent is a checkpoint inhibitor protein. In an embodiment, the therapeutic agent is ipilimumab. In an embodiment, the therapeutic agent is pembrolizumab. In an embodiment, the therapeutic agent is nivolumab. In an embodiment, the therapeutic agent is talimogen laherparebbec. In an embodiment, the therapeutic agent is dermalumab. In an embodiment, the therapeutic agent is daclizumab. In an embodiment, the therapeutic agent is avelumab. In an embodiment, the therapeutic agent is atezolizumab. In an embodiment, the chimeric poxvirus and therapeutic agent are administered in a combined synergistic amount. In an embodiment, the chimeric poxvirus and therapeutic agent are administered concurrently. In an embodiment, the chimeric poxvirus and therapeutic agent are administered sequentially.

In some embodiments, co-administration comprises administering one active agent within 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, or 24 hours of a second active agent (eg, anti-cancer agent). include Co-administration includes administration of the two active agents simultaneously, approximately simultaneously (eg, within about 1, 5, 10, 15, 20 or 30 minutes of each other) or sequentially in any order. In some embodiments, co-administration can be achieved by co-formulation, i.e., preparing a single pharmaceutical composition comprising both active agents. In other embodiments, the active agents may be formulated separately. In another embodiment, active agents and/or adjuvants may be combined or conjugated to one another.

“Anti-cancer agent” is used according to its general and conventional meaning and refers to a composition (eg, compound, drug, antagonist, inhibitor, modulator) having anti-neoplastic properties or the ability to inhibit the growth or proliferation of cells. In some embodiments, the anti-cancer agent is a chemotherapeutic agent. In some embodiments, an anti-cancer agent is an agent identified herein that has utility in a method of treating cancer. In some embodiments, the anti-cancer agent is an agent approved by the FDA or similar regulatory agency outside the United States for the treatment of cancer. Examples of anticancer agents include MEK (eg MEK1, MEK2, or MEK1 and MEK2) inhibitors (eg XL518, CI-1040, PD035901, Selumetinib/AZD6244, GSK1120212/Trametinib, GDC-0973, ARRY -162, ARRY-300, AZD8330, PD0325901, U0126, PD98059, TAK-733, PD318088, AS703026, BAY 869766), alkylating agents (e.g. cyclophosphamide, ifosfamide, chlorambucil, busulfan, mel Phalan, mechlorethamine, uramustine, thiotepa, nitrosourea, nitrogen mustard (eg mechloroethamine, cyclophosphamide, chlorambucil, mayphalan), ethylenimine and methylmelamine (eg For example, hexamethylmelamine, thiotepa), alkyl sulfonates (eg busulfan), nitrosoureas (eg carmustine, lomustine, semustine, streptozocin), triazenes (decarbazine) ), an antimetabolite (e.g. 5-azathioprine, leucovorin, capecitabine, fludarabine, gemcitabine, pemetrexed, raltitrexed, a folic acid analog (e.g. methotrexate), or pyri Midine analogs (e.g. fluorouracil, floxouridine, cytaradine), purine analogs (e.g. mercaptopurine, thioguanine, pentostatin), etc.), plant alkaloids (e.g. vincristine, vinblastine, vinorelbine, vindesine, podophyllotoxin, paclitaxel, docetaxel, etc.), topoisomerase inhibitors (e.g., irinotecan, topotecan, amsacrine, etoposide (VP16), etoposide phosphate, teniposide, etc.), anticancer antibiotics (eg, doxorubicin, adriamycin, daunorubicin, epirubicin, actinomycin, bleomycin, mitomycin, mitoxantrone, plicamycin, etc.), platinum-based compounds or Platinum-containing agents (e.g. cisplatin, oxaloplatin, carboplatin) anthracenediones (e.g. mitoxantrone), substituted ureas (e.g. hydroxuurea), methyl hydrazine derivatives (e.g. procarbazine), adrenocortical inhibitors (eg mitotane, aminoglutethimide), epitodophylotoxins (eg etoposide), antibiotics (eg daunorubicin, doxorubicin, bleomycin), enzymes (eg L-asparaginase), inhibitors of mitogen activated protein kinase signaling (eg U0126, PD98059, PD184352, PD0325901, ARRY-142886, SB239063, SP600125, BAY 43 -9006, Bortmannin, or LY294002, Syk inhibitors, mTOR inhibitors, antibodies (eg rituxan), gosypol, Genasense, polyphenol E, chlorofuscin, all trans-retinoic acid (ATRA) acid), bryostatin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), 5-aza-2'-deoxycytidine, all-trans retinoic acid, doxorubicin, vincristine, etoposide, gemcitabine, imatinib (Gleevec™), geldanamycin, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), flavopiridol, LY294002, bortezomib, trastuzumab, BAY 11-7082, PKC412, PD184352, 20-epi-1, 25 dihydroxyvitamin D3; 5-ethynyluracil; abiraterone; Aclarubicin; acylfulben; adecyphenol; adozelesin; adelsleukin; ALL-TK antagonist; altretamine; ambamustine; amidox; amifostine; aminolevulinic acid; amrubicin; amsacrine; anagrelide; anastrozole; Andrographolide; angiogenesis inhibitors; antagonist D; antagonist G; Antarelix; anti-dorsalizing morphorgenetic protein; antiandrogen, prostate carcinoma; antiestrogens; antineoplastons; antisense oligonucleotides; aphidicolin glycinate; apoptosis gene regulator; apoptosis regulator; apuric acid; Ara-CDP-DL-PTBA; arginine deaminase; asulacrine; atamestan; atrimustine; acinastatin 1; acinastatin 2; acinastatin 3; azasetron; azatoxin; azatyrosine; baccatin III derivatives; balanol; batimastat; BCR/ABL antagonists; benzochlorine; benzostaurosporine; beta lactam derivatives; beta-alletin; betaclamycin B; betulinic acid; bFGF inhibitors; bicalutamide; bisantrene; bisaziridinylspermine; bisnapid; Bistraten A; bizelesin; bread plate; bropyramine; titanium budotium; butionine sulfoximine; calcipotriol; calphostin C; camptothecin derivatives; canary fox IL-2; capecitabine; carboxamide-amino-triazole; carboxyamidotriazole; CaRest M3; CARN 700; cartilage-derived inhibitors; carzelesin; casein kinase (ICOS); Castanosfermine; Cecropin B; set laurellix; clorinth; chloroquinoxaline sulfonamide; cicaprost; cis-porphyrin; cladribine; clomiphene analogues; clotrimazole; colismycin A; colismycin B; combretastatin A4; combretastatin analogs; conagenin; Crambecidin 816; Krisnatol; cryptophycin 8; cryptophycin A derivatives; Curacin A; cyclopentanetraquinone; cycloplatam; cifemycin; cytarabine octosephate; cytolytic factor; cytostatin; dacliximab; decitabine; dehydrodidemnin B; deslaurelin; dexamethasone; dexiphosphamide; dexrazoxane; dexverapamil; diaziquone; Didemnin B; dedox; diethylnorsfermine; dihydro-5-azacytidine; 9-dioxamycin; diphenyl cypyromustine; docosanol; dolasetron; doxyfluridine; droloxifene; dronabinol; Duocarmycin SA; ebselen; decomustine; edelphosine; edrecolomab; eflornithine; elemen; Emitepur; epirubicin; epristeride; estramustine analogs; estrogen agonists; estrogen antagonists; Ethanidazole; etoposide phosphate; exemestane; fadrozole; pajarabine; fenretinide; pilgrass team; finasteride; flavopiridol; plegelastine; fluasterone; fludarabine; Fluorodaonorunisin hydrochloride; forfenimex; formestane; postlysin; fotemustine; gadolinium texapyrin; gallium nitrate; galocitabine; ganirelix; gelatinase inhibitors; gemcitabine; glutathione inhibitors; hepsulfam; heregulin; hexamethylene bisacetamide; hypericin; ibandronic acid; idarubicin; idoxifene; hydra manton; ilmofosin; ilomastat; imidazoacridone; imiquimod; immunostimulatory peptides; insulin-like growth factor-1 receptor inhibitors; interferon agonists; interferon; interleukin; iobenguane; iodoxorubicin; Ipomeanol, 4-; irofract; Irsogladin; isobengazole; isohomohalichondrin B; itacetron; Jasplakinolide; kahalalid F; lamellarin-N triacetate; lanreotide; Raynamycin; lengrastim; retinan sulfate; leptolstatin; Letrozole; leukemia inhibitory factor; leukocyte alpha interferon; leuprolide + estrogen + progesterone; leuprorelin; bebamisol; liarosol; linear polyamine analogs; lipophilic disaccharide peptides; lipophilic platinum compounds; lysoclinamide 7; lobaplatin; lombrycin; lometrexol; Ronidamine; rosoxantrone; lovastatin; rock soribine; rurtotecan; lutetium texapyrin; lysophylline; soluble peptides; maytansine; mannostatin A; marimastat; masoprocol; maspin; matrilysin inhibitors; matrix metalloproteinase inhibitors; menogaryl; Merbaron; metrelin; methioninase; metoclopramide; MIF inhibitors; mifepristone; miltefosine; Mirimos team; mismatched double-stranded RNA; mitoguazone; mitolactol; mitomycin analogs; mitonapid; mitotoxin fibroblast growth factor-saporin; mitoxantrone; moparothene; Molgramos team; monoclonal antibody, human chorionic gonadotropin; monophosphoryl lipid A+Myobacterium cell wall sk; furdamole; multi-drug resistance gene inhibitor; multiple tumor suppressor 1 based therapies; mustard anti-cancer agent; micaroxide B; Mycobacterium cell wall extract; Myriaphoron; N-acetyldinaline; N-substituted benzamides; nafarelin; nagres tip; naloxone+pentazocine; napabine; naphterpine; nartograstim; nedaplatin; Nemorubicin; neridronic acid; neutral endopeptidase; nilutamide; nisamicin; nitric oxide regulators; nitroxide antioxidants; nitruline; O6-benzylguazine; octreotide; oxynone; oligonucleotide; onapristone; ondansetron; ondansetron; aurasin; oral cytokine inducers; ormaplatin; osaterone; oxaliplatin; oxaunomycin; Palauamine; palmitoylizoxin; pamidronic acid; panaxytriol; panomiphene; parabactin; pazeliptin; pegaspargase; feldsyn; sodium pentosan polysulfate; pentostatin; pentrozole; perflubron; perphosphamide; perillyl alcohol; phenazinomycin; phenylacetate; phosphatase inhibitors; fishvanyl; pilocarpine hydrochloride; pirarubicin; pyritrexime; placetin A; placetin B; plasminogen activator inhibitors; platinum complex; platinum compounds; platinum-triamine complexes; porfimer sodium; porphyromycin; prednisone; propyl bis-acridone; prostaglandin J2; proteasome inhibitors; protein A based immune modulator; protein kinase C inhibitors; protein kinase C inhibitor, microalgal; protein tyrosine phosphatase inhibitors; purine nucleoside phosphorylase inhibitors; Purpurin; pyrazoloacridine; pyridoxylated hemoglobin polyoxyethylene conjugates; raf antagonists; raltitrexed; ramoseterone; ras farnesyl protein transferase inhibitors; ras inhibitors; ras-GAP inhibitors; retheliptin dimethylation; rhenium Re 186 detidronate; lyzoxine; ribozymes; RII Retinamide; rogletimide; Rohitukhin; Romurtide; Roquinimex; rubiginone B1; luboxil; Safin Gol; sinetopine; SarCNU; Sarcophytol A; sargramos team; Sdi 1 mimetics; semustine; senescence derived inhibitor 1; sense oligonucleotide; signal transduction inhibitors; signal transduction modulators; single chain antigen binding protein; sizofuran; sotrizoic acid; sodium borocaptate; sodium phenylacetate; Solverol; somatomedin binding protein; sonermin; sparphosic acid; spicamycin D; spiromustine; splenopentin; spongistatin 1; squalamine; stem cell inhibitors; stem cell division inhibitors; stipiamid; stromelish inhibitors; sulfinosine; superactive vasoactive intestinal peptide antagonists; suradista; Suramine; swain sonin; synthetic glycosaminoglycans; talimustine; tamoxifen methiodide; tauromustine; tazarotene; tecogallan sodium; Tegapur; tellurapyrylium; telomerase inhibitors; temoporfin; temozolomide; teniposide; tetrachlorodecoxide; tetrazomine; Taliblastin; thiocorraline; thrombopoietin; thrombopoietin mimetics; timalfacin; thymopoietin receptor agonists; timotrinan; thyroid stimulating hormone; etiopuruline ethyl tin; tirapazamine; titanocene bichloride; topsentin; toremifene; totipotent stem cell factor; translation inhibitors; tretinoin; triacetyluridine; triciribine; trimetrexate; triptorelin; tropisetron; turosteride; tyrosine kinase inhibitors; Tyrphostin; UBC inhibitors; uvenimex; genitourinary sinus-derived growth inhibitory factor; urokinase receptor antagonists; barreotide; barioline B; vector systems, erythroid gene therapy; Velaresol; veramine; Verdin; verteporfin; vinorelbine; vinzaltine; nontaxin; vorozol; zanoterone; Geniplatin; Zillascove; and ginostatin stimalamer, adriamycin, dactinomycin, bleomycin, vinblastine, cisplatin, acivicin; Aclarubicin; acodazole hydrochloride; acronin; adozelesin; aldesleukin; altretamine; ambomycin; amethanthron acetate; aminoglutethimide; amsacrine; anastrozole; anthramycin; asparaginase; asperlin; azacytidine; azetepa; azotomycin; batimastat; benzodepa; bicalutamide; bisantrene hydrochloride; bisnapid dimesylate; bizelesin; bleomycin sulfate; brequinard sodium; bropyramine; Busulfan; cactinomycin; calosterone; carasemide; carbetimers; carboplatin; carmustine; carubicin hydrochloride; carzelesin; cedefingol; chlorambucil; sirolemycin; cladribine; chrysantol mesylate; cyclophosphamide; cytarabine; dacarbazine; daunorubicin hydrochloride; decitabine; dexomaplatin; dezaguanine; dezaguanine mesylate; diaziquone); doxorubicin; doxorubicin hydrochloride; droloxifene; droloxifene citrate; dromostanolone propionate; duazomycin; edatrexate; eflornithine hydrochloride; elsamitrucine; enroplatin; enpromate; epipropidin; epirubicin hydrochloride; erbulozole; esorubicin hydrochloride; estramustine; estramustine phosphate sodium; Ethanidazole; etoposide; etoposide phosphate; etoprine; fadrozole hydrochloride; pajarabine; fenretinide; floxuridine; fludarabine phosphate; fluorouracil; fluorocitabine; phosquidone; postlysine sodium; gemcitabine; gemcitabine hydrochloride; hydroxyurea; idarubicin hydrochloride; ifosfamide; ilmofosin; interleukin II (including recombinant interleukin II, or rlL.sub.2), interferon alpha-2a; interferon alpha-2b; interferon alpha-n1; interferon alpha-n3; interferon beta-1a; interferon gamma-1b; iproplatin; irinotecan; irinotecan hydrochloride; lanreotide acetate; Letrozole; leuprolide acetate; Liarozole hydrochloride; lometrexol sodium; lomustine; rosoxantrone hydrochloride; masoprocol); maytansine; mechlorethamine hydrochloride; megestrol acetate; melengestrol acetate; melphalan; menogaryl; mercaptopurine; methotrexate; methotrexate sodium; methoprine; meturedepa; mitindomide; mitocarcin; Mitochromin; Mitogiline; mitomaxin; mitomycin; Mytosper; mitotane; mitoxantrone hydrochloride; mycophenolic acid; nocodazole; nogalamycin; ormaplatin; oxysuran; pegaspargase; pelomycin; pentamustine; peflomycin sulfate; perphosphamide; piphobroman; piposulfan; pyroxantrone hydrochloride; plicamycin; flomestan; porfimer sodium; porphyromycin; prednimustine; procarbazine hydrochloride; puromycin); puromycin hydrochloride; pyrazopurine; riboprine; rogletimide; Safin Gol; safingol hydrochloride; semustine; Simtrazen; sparphosate sodium; sparsomycin; spirogermanium hydrochloride; spiromustine; spiroplatin; streptonigrin; streptozocin; sulopenner; Thalisomycin; tecogallan sodium; Tegapur; teloxantrone hydrochloride; temoporfin; teniposide; teroxirone; testolactone; thiamiprine; thioguanine; thiotepa; thiazopurine; tirapazamine; toremifene citrate; trestolone acetate; triciribine phosphate; trimetrexate; trimetrexate glucuronate; triptorelin; tubulosole hydrochloride; uracil mustard; Uredepa; barreotide; verteporfin; vinblastine sulfate; vincristine sulfate; vindesine; vindesine sulfate; vinepidine sulfate; empty glycinate sulfate; vinlurosine sulfate; vinorelbine tartrate; binrosidine sulfate; vinzolidine sulfate; vorozol; Geniplatin; ginostatin; zorubicin hydrochloride, agents that arrest cells in G2-M phase and/or modulate microtubule formation or stability (e.g., Taxol™ (i.e., paclitaxel), Taxotere™, the taxane backbone Compounds comprising, erbulozole (i.e. R-55104), dolastatin 10 (i.e. DLS-10 and NSC-376128), mibobulin isethiotate (i.e. as CI-980), vincristine, NSC- 639829, discodermolide (ie as NVP-XX-A-296), ABT-751 (Abbott, ie E-7010), althortin (eg althortin A and althortin C), Spongistatin (e.g., spongistatin 1, spongistatin 2, spongistatin 3, spongistatin 4, spongistatin 5, spongistatin 6, spongistatin 7, spongistatin 8, and spongistatin gistatin 9), semadotin hydrochloride (i.e. LU-103793 and NSC-D-669356), epothilones (e.g. epothilone A, epothilone B, epothilone C (i.e. deoxyepothilone) A or dEpoA), epothilone D (i.e., KOS-862, dEpoB, and desoxyepothilone B), epothilone E, epothilone F, epothilone B N-oxide, epothilone A N-oxide, 16-aza-epothilone B, 21-aminoepothilone B (i.e. BMS-310705), 21-hydroxyepothilone D (i.e. desoxyepothilone F and dEpoF), 26-fluoroepo Tilon, Auristatin PE (ie NSC-654663), Solblidotin (ie TZT-1027), Vincristine Sulfate, Cryptophycin 52 (ie LY-355703), Vitilebuamide, Tubulysin A, Canadensol, Centaureidine (i.e. NSC-106969), Oncocidin A1 (i.e. BTO-956 and DIME), Fijianolide B, Raulimalide, Narcosine (also known as NSC-5366), NASCAR Pin, hemiastellin, vanadocen acetylacetonate, monasatrol, inanosine (i.e. NSC-698666), eleuterobin (e.g. K desmethyl eleuterobin, desaethyl eleuterobin, iso eleuterobin A, and Z-eluterobin), carivaeoside, carivaeoline, halichondrin B, diazonamide A, tacalonolide A, diozostatin, (-)-phenylahistine ( i.e. NSCL-96F037), myoseverin B, resverastatin phosphate sodium, steroids (e.g. dexamethasone), finasteride, aromatase inhibitors, gonadotropin-releasing hormone agonists (GnRH), e.g. e.g. goserelin or leuprolide, adrenocorticosteroids (e.g. prednisone), progestins (e.g. hydroxyprogesterone caproate, megestrol acetate, medroxyprogesterone acetate), estrogens (e.g. diethylstilbestrol, ethinyl estradiol), antiestrogens (eg tamoxifen), androgens (eg testosterone propionate, fluoxymesterone), antiandrogens (eg flutamide) , immunostimulants (e.g., Bacillus Calmette-Guerin, levamisole, interleukin-2, alpha-interferon, etc.), monoclonal antibodies (e.g., anti-CD20, anti-HER2, anti-CD52) , anti-HLA-DR, and anti-VEGF monoclonal antibodies), immunotoxins (e.g., anti-CD33 monoclonal antibody-calicheamicin conjugates, anti-CD22 monoclonal antibody-pseudomonas exotoxin conjugates, etc.), Radiation immunotherapy (eg, anti-CD20 monoclonal antibodies conjugated to ¹¹¹ In, ⁹⁰ Y, or ¹³¹ I, etc.), triptolide, homoharringtonine, dactinomycin, doxorubicin, epirubicin, topotecan, itraconazole , vindesine, cerivastatin, vincristine, deoxyadenosine, sertraline, pitavastatin, irinotecan, clofazimine, 5-nonyloxytryptamine, vemurafenib, dabrafenib, erlotinib, gefitinib , EGFR inhibitors, epidermal growth factor receptor (EGFR)-targeted therapies or treatments (e.g., gefitinib (Iressa™), erlotinib (Tarceva™), cetuximab) (Erbitux™), lapatinib (Tykerb™), panitumumab (Vectibix™), vandetanib (Caprelsa™), afatinib/BIBW2992, CI-1033/ Canertinib, neratinib/HKI-272, CP-724714, TAK-285, AST-1306, ARRY334543, ARRY-380, AG-1478, dacomitinib/PF299804, OSI-420/desmethyl erlotinib, AZD8931 , AEE788, pelitinib/EKB-569, CUDC-101, WZ8040, WZ4002, WZ3146, AG-490, XL647, PD153035, BMS-599626.

VII. detection method

In another aspect is a method of detecting cancer in a subject in need thereof, comprising contacting a cancer cell with a chimeric poxvirus described herein (including embodiments thereof) and allowing the chimeric poxvirus to replicate, thereby detecting the cancer cell. A method including is provided. In an embodiment, a chimeric poxvirus comprises a nucleic acid sequence encoding a detectable molecule. In an embodiment, the detectable moiety encoding nucleic acid sequence encodes a fluorescent moiety. In an embodiment, the detectable moiety encoding nucleic acid sequence encodes m.chery. In an embodiment, the detectable moiety encoding nucleic acid sequence encodes Emerald. In an embodiment, the detectable moiety encoding nucleic acid sequence encodes a firefly luciferase. In an embodiment, the cancer cells are present in the subject. In embodiments, the subject is a mammal. In embodiments, the subject is a human.

Example

The following examples are provided to illustrate but not to limit the claimed invention.

Example 1. Novel potent novel for oncolytic immunotherapy of cancer chimera poxvirus

Cancer is the second leading cause of death in the United States. In recent years, significant advances have been made in cancer immunotherapy, including immune checkpoint inhibitors, T cells with chimeric antigen receptors, and oncolytic viruses.

Oncolytic viruses are naturally occurring or genetically modified viruses that infect cancer cells without damaging healthy cells, replicate within them and eventually kill the cancer cells (1,2). A recently completed phase III clinical trial of oncolytic herpes simplex virus T-VEC in 436 patients with unresectable stage IIIB, IIIC, or IV melanoma compared with 2.1% in patients receiving GM-CSF. Patients receiving T-VEC have been reported to meet the primary endpoint with a sustained response rate of 16.3% (3). Based on the results of this clinical trial, the FDA approved T-VEC on October 27, 2015. FDA approval of the first oncolytic virus paved the way for a promising field.

Adenovirus, herpes simplex virus 1, Newcastle disease virus, reovirus, measles virus, coxsackievirus, Seneca Valley virus and vaccinia Oncolytic viral constructs from at least 8 different species, including Nia virus, were tested in several phases of clinical trials. In cancer patients, oncolytic viruses have been found to be well tolerated. However, the clinical benefit of oncolytic viruses as a monotherapy is limited (5). Because of concerns about the safety of oncolytic viruses, only highly attenuated oncolytic viruses (naturally non-toxic or attenuated through genetic engineering) have been used in both preclinical and clinical trials. Now that the safety of oncolytic viruses is well established, it is time to design and test oncolytic viruses with maximal antitumor efficacy. Oncolytic viruses with strong oncolytic effects will release tumor antigens abundantly and exert strong immunotherapeutic effects.

Vaccinia virus, the prototype of the poxvirus family, was used as a smallpox vaccine to eradicate smallpox, which is estimated to have killed 500 million people in the 19th and 20th centuries alone. Therefore, it is arguably the most successful biotherapeutic agent. The safety of vaccinia virus has been well established in millions of people worldwide. Vaccinia virus is also the first oncolytic virus to show viral oncolysis in the laboratory. As an oncolytic virus, vaccinia virus has been tested in many clinical trials and has been shown to be well tolerated in patients with advanced stage cancer (2). Several studies show that in terms of oncolytic activity, it is superior to adenovirus, which is one of the best-studied oncolytic virus species and the first oncolytic virus approved for cancer treatment in China (7) (6). Besides vaccinia virus, other members of the poxvirus family have also been tested as oncolytic viruses, including raccoonpox virus (8), sheeppox virus (9), and myxoma virus (10).

Chimeric poxviruses are superior to individual wild-type viruses because they have the potential to combine the advantageous characteristics of different viral species. Because orthopoxviruses and parapoxviruses are antigenically distinct, the potent chimeric orthoviruses and potent parapoxviruses generated in this study could possibly be combined in the same treatment regimen to achieve maximum therapeutic efficacy. Applicants have generated pools of chimeric orthopoxviruses and chimeric parapoxviruses. Several chimeric orthopoxvirus and parapoxvirus isolates showed superior killing ability in the NCI 60 cancer cell line panel compared to individual parental wild-type viruses.

Generation of chimeric virus pools and isolation of each chimeric virus. Vaccinia virus strain Brighton, raccoon fox virus strain Herman, harepox virus strain Utrecht, and vaccinia virus strains WR, IHD, Elstree, CL, Redlet-Illinois and AS CV with a multiplicity of infection (MOI) of 0.01 per virus. -1 cells were coinfected to generate chimeric orthopoxvirus pools. To generate chimeric parapoxvirus pools, MDBK cells were coinfected with both pox virus strain NZ2 and pseudo vaccinia virus strain TJS at an MOI of 0.1. Applicant's preliminary experiments show that CV-1 cells are susceptible to all orthopoxviruses used in this study, and both pox virus and pseudopox virus infect MDBK cells and form plaques on them.

100 chimeric orthopoxvirus plaques and 100 chimeric parapoxvirus plaques were collected from CV-1 cells infected with the chimeric orthopoxvirus pool and MDBK cells infected with the chimeric parapoxvirus pool, respectively. These 200 plaques were further plaque-purified more than twice on each cell to obtain individual chimeric virus isolates purified into 200 clones. Virus #14-113 is a chimeric orthopoxvirus isolate, and virus #114-213 is a chimeric parapoxvirus isolate.

Identification of novel potent chimeric poxvirus isolates by high throughput screening in the NCI-60 cell line. The tumor cell killing activity of 200 chimeric orthopoxvirus and chimeric parapoxvirus isolates along with 11 parental virus strains and two control oncolytic viruses (GLV-1h68 and OncoVEX GFP) were evaluated and compared in a panel of NCI-60 cell lines. (Table 1). GLV-1h68 is one of the best-studied oncolytic vaccinia viruses and is currently in clinical development. OncoVEX GFP is oncolytic herpes simplex virus-1 and has the same backbone as T-VEC, the first oncolytic virus approved by the FDA. Each cell line was infected with each virus at an MOI of 0.01. Cell viability was measured using the MTS assay 96 hours after infection. In order to allow strong viral isolates to stand out, the amount of virus used in this high-throughput screening experiment (MOI 0.01) was intentionally kept low and cell death was observed in adherent cell lines (most cell lines in the NCI-60 panel are adherent cells). Optimized for comparison. However, this viral load was too low to show significant and consistent cell death in floating cell lines. Therefore, the results of the six leukemia cell lines were not included in the analysis for virus comparison.

<Table 1>

Of the 100 new chimeric orthovirus isolates, isolates #17 (SEQ ID NO: 3) and #33 (SEQ ID NO: 1) were cells significantly superior to the 9 parental orthovirus strains and 2 control viruses in the NCI-60 solid tumor cell line. showed apoptosis (FIG. 1). Among the 100 new parapoxvirus isolates, isolate #189 (SEQ ID NO: 2) stood out, which showed significantly better cell death than the two parental parapoxvirus strains and the control virus (FIG. 2). All three novel chimeric virus isolates (#17, #33 and #189) induced significant cell death in most NCI-60 solid cancer cell lines at a low MOI of 0.01. In general, orthopoxvirus strains and chimeric orthopoxvirus isolates were more potent than parapoxvirus strains and chimeric parapoxvirus isolates in killing cancer cells at MOI as low as 0.01.

Genome sequencing of #33 and #189. Genomic DNA of novel poxvirus isolates #33 and #189 were isolated from purified virions and subjected to next-generation sequencing using an Illumina Hiseq 2500 with >1000-fold coverage. Gaps were amplified by PCR and sequenced by Sanger sequencing. 189,415 base pairs (bp) of the #33 genome were completely sequenced, while 138,203 bp of the 189 genome were obtained. An initial BLAST against GenBank indicated that the genomic sequences of both #33 and #189 were not identical to any genomic sequences in GenBank. #33 is closer to vaccinia virus strains than to other orthopoxviruses. #189 is very close to strain NZ2 of the sheeppoxvirus, one of the parental parapoxviruses. The nucleotide sequences of all ORFs identified in the sheeppox virus strain NZ2 are the same as in #189. Compared to the sheeppox virus NZ2, a "G" is inserted at position 6755 in the genome of #189. The inverted terminal repeat region contains one copy of the deleted repeat element and one copy of another repeat element inserted into genome #189. Collectively, both #33 and #189 represent novel and unique poxvirus isolates.

Methods and Materials: Cell Lines: All cancer cell lines were cultured in RPMI-1640 (Mediatech, Manassas, Va.). African green monkey kidney fibroblasts (CV-1) and bovine kidney epithelial cells (MDBK) were obtained from the American Type Culture Collection (ATCC, Rockville, MD) and cultured in DMEM (Mediatech, Manassas, VA). All media were supplemented with 10% FBS (Mediatech, Manassas, VA) and 1% penicillin-streptomycin solution (Mediatech, Manassas, VA). Cells were cultured at 37° C. under 5% CO ₂ .

Viruses: vaccinia virus strain Brighton, raccoonpox virus strain Herman, harepox virus strain Utrecht, vaccinia virus strain WR, IHD, Elstri, CL, Radle-Illinois and AS, sheeppox virus strain NZ2 and pseudovax virus strain TJS was purchased from ATCC. All orthopoxvirus strains were cultured and titers were measured in CV-1 cells, and parapoxvirus strains were cultured and titers were measured in MDBK cells.

chimera Orthopoxviruses and Chimeras Generation of parapoxvirus pools and isolation of chimeric virus isolates of individual clones: vaccinia virus strain Brighton, raccoon fox virus strain Herman, harepox virus strain Utrecht, and vaccinia virus strains WR, IHD, Elstree, CL, Ledle- Chimeric orthopoxvirus pools were generated by coinfecting CV-1 cells with a multiplicity of infection (MOI) of 0.01 per virus in the ileal membrane and AS. To generate chimeric parapoxvirus pools, MDBL cells were co-infected with sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS at an MOI of 0,1. Infected cells were harvested 3 days after infection. The initial chimeric orthopoxvirus pool was passaged 3 additional times in CV-1 cells at MOI 0.1, and the initial chimeric parapoxvirus pool was passaged 3 more times in MDBK cells at MOI 0.1. 100 chimeric orthopoxvirus plaques and 100 chimeric parapoxvirus plaques were collected from CV-1 cells infected with the final chimeric orthopoxvirus pool and MDBK cells infected with the final chimeric parapoxvirus pool, respectively. These 200 plaques were further plaque purified more than twice on each cell to obtain individual chimeric virus isolates purified into 200 clones.

High-efficiency screening: NCI-60 cancer cell line and a panel of pancreatic cancer cell lines including PANC-1, MIA-PaCa2, BxPC3, FG, Capan-2 and Su.86.86 were 96 using an epMotion 5075 liquid handler (Eppendorf) under sterile conditions. Distribute into well plates (3000 cells/well for solid tumor cell lines and 5000 cells/well for leukemia cell lines), 37°C, 5% (v/v) CO₂ Incubated overnight under Cells were then infected at an MOI of 0.01 with 200 chimeric orthopoxvirus and chimeric parapoxvirus isolates along with 11 parental virus strains and two control oncolytic viruses, GLV-1h68 and OncoVEX GFP. Cell viability was determined using the MTS assay (Promega) 96 hours after infection. Absorbance was measured at 490 nm using an automated BMG PHERAstar plate reader (BMG Labtech). Each experiment was performed in duplicate. Cell viability of mock-infected cells was set to 100%.

Viral cytotoxicity in gastric cancer cell lines: MKN-45, OCUM-2M and KATO-3 cells were seeded in 96-well plates at a concentration of 3,000 cells/well and incubated overnight at 37°C, 5% (v/v) CO ₂ . Cells were infected with #33, #189, GLV-1h68 and OncoVEX GFP at MOIs of 0.01, 0.1 and 1. Cell viability was monitored daily for 4 days using the MTS assay at 37° C. under 5% (v/v) CO ₂ .

Genomic Sequencing: Genomic DNA of #33 and #189 was extracted from purified virions using the Wizard Genomic DNA Purification kit (Promega) and fragmented by sonication. Libraries were prepared using the KAPA LTP library preparation kit. Sequencing was performed using an Illumina Hiseq 2500.

Example 2. High-throughput screening in pancreatic cancer cell lines

The NCI-60 cancer cell line contains only solid cancers of 8 different organs (see Table 1). To investigate whether the results of the NCI-60 cancer cell line are reproducible in solid cancers of other organ origin, six pancreatic cancer cell lines (BxPC3, FG, MIA PaCa-2, Capan-2, PANC-1 and SU.86.86) were transfected into the NCI-60 cancer cell line. Cell lines were infected at MOI 0.1 with the same virus used in high-throughput screening. Cell viability was measured again using the MTS assay 96 hours after infection. Chimeric orthopoxvirus isolates #17 and #33 showed the best cell death among all chimeric orthopoxvirus isolates, while chimeric parapoxvirus isolate #189 showed the best cell death among all chimeric parapoxvirus isolates. All of them were superior to their respective parental virus strains and control viruses, GLV-1h68 and OncoVEX GFP, in killing pancreatic cancer cell lines, as shown in Table 2 and [Figure 3] and [Figure 4]. Thus, the results of the NCI-60 cancer cell line were reproduced very well in the pancreatic cancer cell line panel.

<Table 2>

Example 3. New chimera orthopox virus isolate #33 and chimera parapox virus isolate #189 exhibits strong apoptosis in gastric cancer cell lines. indicate

Based on the results of high-throughput screening from the NCI-60 cancer cell line and pancreatic cancer cell line panel, novel chimeric orthopoxvirus isolate #33 and chimeric parapoxvirus isolate #189 were selected for further characterization. The tumor cell killing activity of isolates #33 and #189 was further investigated in three gastric cancer cell lines. MKN-45, OCUM-2M and KATO-3 cells were infected with #33, #189, GLV-1h68 and OncoVEX GFP at MOIs of 0.01, 0.1 and 1. Cell viability was monitored daily for 4 days using the MTS assay. MKN-45 and OCUM-2M cell lines were most sensitive to #33, moderately sensitive to OncoVEX GFP, and least sensitive to GLV-1h68. While KATO-3 was most sensitive to OncoVEX GFP at a low MOI of 0.01, #33, #189, and OncoVEX GFP killed KATO-3 cells equally well at higher MOIs (0.1 and 1). KATO-3 cells were the least sensitive to GLV-1h68. Overall, #33 killed gastric cancer cell lines most efficiently, whereas GLV-1h68 killed gastric cancer cell lines least efficiently (FIG. 5A-FIG. 5C).

As reported in Table 3, the 90 genes present in all ChPVs sequenced are listed along with their function when known. The gene is named after the VACV-COP counterpart. Asterisks (*) indicate genes that are also present in both EnPVs. Table 3 is described in Gubser, C., Hue, S., Kellam, P., and Smith, G.L. (2004). Poxvirus genomes: a phylogenetic analysis. J Gen Virol 85, 105-117), which is incorporated herein by reference in its entirety for all purposes.

<Table 3>

It is understood that the examples and embodiments described herein are for illustrative purposes only, and that various modifications or alterations in light thereof will be suggested to those skilled in the art and are to be included within the spirit and understanding of this application and the scope of the appended claims. All publications, patents and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes.

Example 4. Novel as oncolytic immunotherapy in triple negative breast cancer chimera parapox virus HOV -189

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a high recurrence rate and a poor prognosis. Applicants describe herein a novel, genetically modified parapoxvirus that efficiently kills TNBC.

Method: A novel chimeric parapoxvirus (HOV-189) was generated through homologous recombination and identified through high-throughput screening. Cytotoxicity was assayed in vitro in four TNBC cell lines. Viral replication was investigated via a standard plaque assay. Orthotopic TNBC xenografts were generated by MDA-MB-468 implantation in the second and fourth mammary fat pads of athymic nude mice and treated with virus.

Results: HOV-189 exhibited dose-dependent cytotoxicity at low multiplicity of infection (MOI), with >90% cell death after 6 days of treatment. A significant reduction in tumor size compared to control was observed 2 weeks after intratumoral injection at doses as low as 10 ³ PFU (P < 0.01). In addition, the abscopal effect (shrinkage of uninjected distant tumors) was clearly demonstrated.

CONCLUSIONS: HOV-189 exhibited effective cytotoxicity in vitro and potent antitumor effects in vivo at doses as low as 10 ³ PFU. This is data encouraging clinical development of this very potent agent against TNBC.

introduction

Approximately 12-20% of the million newly diagnosed breast cancer cases worldwide each year are triple negative, meaning they lack expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). ¹¹ Triple-negative breast cancer (TNBC) has a poor clinical outcome due to both its aggressive nature and the absence of effective targeted therapies. TNBC patients have a higher risk of developing recurrent and metastatic disease within the first 5 years after diagnosis than non-TNBC patients. ¹²

Currently, the centerpiece of adjuvant therapy for TNBC is cytotoxic chemotherapy, but research into poly(ADP-ribose) polymerase 1 (PARP1) inhibitors, PI3K inhibitors, MEK inhibitors, and programmed death ligand 1 (PD-L1) inhibitors There has been intensive research and development of targeted therapies, including ^{11 ,13}

Immunotherapy has long been an area of research for many types of cancer, including breast cancer. TNBC exhibits increased genetic instability, a high proportion of neoantigens, and a high frequency of tumor infiltrating lymphocytes (TIL) in the microenvironment, making TBNC more immunogenic than non-triple negative diseases. ¹⁴ These factors make TNBC a good candidate for immunotherapy. Applicants previously investigated an oncolytic vaccinia virus with antitumor effects in the TNBC model. Here we present data for a novel chimeric parapoxvirus that is effective in the TNBC model both in vitro and in vivo.

method

cell cultures and cell lines. Human triple-negative breast cancer cell lines MDA-MB-231 (kindly provided by Dr. Sang-Gil Nam, City of Hope), MDA-MB-468 (kindly provided by Dr. John Lim, City of Hope), BT549 (Dr. Lim) and Hs578T (Dr. Lim) was cultured in RPMI 1640 (Corning, Corning, NY) supplemented with 10% fetal bovine serum (FBS) and 100 IU/ml streptomycin and penicillin. All TNBC lines were tested and certified by Genetica Cell Line Testing (Burlington, NC). African green monkey kidney fibroblasts (CV-1) and MDBK cells were obtained from the American Type Culture Collection (Manassas, VA) and cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% FBS and 100 IU/ml streptomycin and penicillin. , Corning, Corning, NY). All cells were cultured at 37°C in a 5% CO ₂ humidified incubator.

chimera Development and selection of parapoxviruses . To generate chimeric parapoxvirus pools, MDBK cells were coinfected with sheep pox virus strain NZ2 (ATCC) and pseudo vaccinia virus strain TJS (ATCC). Infected cells were harvested 3 days after infection. 100 chimeric parapoxvirus plaques were harvested from MDBK cells infected with the chimeric parapoxvirus pool. These 100 plaques were further plaque-purified in MDBK cells more than twice to obtain individual chimeric virus isolates purified into 100 clones, which were subjected to high-throughput screening in the NCI-60 cell line along with the parental virus. For this study, the isolate HOV-189, which demonstrated the strongest tumor destruction against the NCI-60 cell line, was selected.

Cytotoxicity assay. Cells were seeded in 96-well plates at 1000 cells/well for MDA-MB-231, BT549 and Hs578T and 3000 cells/well for MDA-MB-468 and incubated overnight. Cells were infected with each virus at MOIs of 0.1, 1, 10 for MDA-MB-231 and 0.01, 0.1, 1 for MDA-MB-468, BT549, and Hs578T. Cell viability was measured in duplicate at 490 nm using CellTiter 96 Aquas One solution (Promega, Madison, Wis.) every 24 h for 1 to 6 days on a spectrophotometer (Tecan Spark 10M, Mannedorf, Switzerland) in triplicate. did

Virus replication assay. Viral replication in TNBC was quantified using a standard plaque assay. Cells were plated in 6-well plates in 2 ml culture medium until confluence and then infected with each virus at an MOI of 0.01. Cells were harvested in triplicate for 3 consecutive days. MDBK cells were infected with serial dilutions of samples treated with HOV-189 in 24 well plates.

Stereotactic Xenograft Model. 10 ⁷ MDA-MB-468 cells with 6 mg/ml Matrigel (Corning) were seeded in 26 Hsd:Athymic Nude- Foxn1 ^nu female nude mice at 12 weeks of age (Envigo, Indianapolis, IN). were injected into the second and fourth mammary fat pads. When tumors reached approximately 100 to 150 mm ³ in size, mice were randomized and tumors were treated with PBS alone (n = 4), 10 ³ PFU in 50 μl PBS (n = 6), 10 ⁴ PFU (n = 6), or 10 ⁵ PFU (n = 7) were injected intratumorally. The amount of change in tumor size was not significantly different between the groups before treatment. Tumor size was then measured every 3 days for 6 weeks. Tumor volume was calculated according to the formula: V ( mm ³ ) = (4/3) x (π) x (a/ 2) ² x (b/2) , where a is the minimum diameter and b is the maximum diameter. . Seven days after intratumoral injection, 2-4 mice per group were sacrificed, tumors and organs (lung, heart, liver, kidney, spleen, ovary, brain) were quenched in liquid nitrogen and further histopathological staining, immunofluorescence It was used for histochemical staining and viral plaque analysis. For the remaining 3 mice, only the second mammary tumor was treated with 10 ⁵ PFU in 50 μl PBS to observe if there was an effect on the fourth uninjected mammary tumor. After 2 weeks of treatment, both tumors were harvested and viral titers were determined in each.

result

HOV -189 effectively kills TNBC in vitro in a time- and dose-dependent manner . Given the heterogeneous nature of TNBC, two cell lines of metastatic origin (MDA-MB-231 and MDA-MB-468) and two cell lines of non-metastatic origin (Hs578T and BT549) were treated with HOV-189 at MOIs ranging from 0.01 to 10. It was treated for 6 days. HOV-189 most effectively killed Hs578T (LD50: MOI 0.396 at 96 hours) and MDA-MB-468 (LD50, MOI 0.185) with >80% cell death at day 6 when treated with an MOI of 1 (Figure 6a and Fig. 6c). Although LD50 was higher for BT549 and MDA-MB-231 (LD50, MOI 1.636 and MOI 1.712, respectively), MDA-MB-231 data showed that increasing concentrations of HOV-189 resulted in >90% cell death at MOI 10 after 6 days. shows this happening (Fig. 6d).

HOV -189 replicates in TNBC in vitro . Viral replication was assessed in all four TNBC cell lines by standard plaque assay of infected cells collected over 3 days. Efficient viral replication occurred in BT549, Hs578T and MDA-MB-231 at an MOI of 0.01, with maximal replication occurring in a period of 24 to 48 hours (FIG. 7). However, although effective cytotoxicity was shown at low MOI, replication of HOV-189 in MDA-MB-468 was slow at MOI 0.01. In the MDA-MB-468 strain, viral replication was enhanced by increasing the concentration to an MOI of 10 (FIG. 7).

Intratumoral HOV -189 injection is stereotactic without significant virological toxicity Effectively reduces tumor size in TNBC xenografts . MDA-MB-468 cells were transplanted into the second and fourth mammary fat pads of athymic nude mice to create stereotactic xenografts. Both tumors were injected intratumorally with either PBS or HOV-189 (10 ³ PFU, 10 ⁴ PFU or 10 ⁵ PFU). All groups treated with HOV-189 showed a significant reduction in relative tumor size compared to the PBS-treated control group up to 13 days after treatment, and this treatment effect persisted for 6 weeks after injection (FIG. 8). Intratumoral injection was well tolerated with no significant virological toxicity in mice, as evidenced by no significant weight loss in the treated groups compared to the control group (FIG. 9).

HOV -189 biodistribution at 1 and 6 weeks post treatment shows unique tumor specificity in vivo. One and six weeks after HOV-189 injection, 2 to 4 mice from each group were sacrificed for virus biodistribution analysis. Viral titers in infected tumor tissues showed a 2 log higher HOV-189 titer than other organs at both time points, reflecting the natural affinity of HOV-189 for cancer cells compared to normal cells (Table 4). Independent of the injected tumor tissue, HOV-189 was only detected in heart and lung tissue at 1 week post-injection and in lung tissue at 6 weeks post-injection, correlating with the absence of significant systemic toxicity observed.

Immunofluorescence imaging confirmed infection and replication of HOV -189 in stereotactic xenograft models. One week after HOV-189 injection, immunofluorescence detection of a polyclonal antibody to sheeppox virus demonstrates viral infection of tumor tissues treated with 10 ⁵ PFU of HOV-189 per tumor compared to controls ( FIGS. 10A and 10B ). . In addition, the pattern of antibody detection merged with DAPI counterstaining is consistent with active replication in the viral factories, as both pox virus antibodies are only localized to extranuclear regions (Fig. 10c).

Intratumoral HOV -189 injection produces tumor suppressive effects in distant uninjected tumors. Three animals were treated with 10 ⁵ PFU of HOV-189 only in the second mammary tumor and left untreated in the fourth mammary tumor. Tumor size was measured every 3 days compared to the PBS treated control group, and viral titers were quantified by standard plaque assay at the end of 2 weeks. Relative tumor size increased in the initially injected tumor group (possibly due to the trauma of the injection itself), but decreased significantly (p<0.05) compared to the control group until day 13, with tumor size decreasing after 6 days. The relative tumor size of the non-injected tumor group remained stable even though it was never directly treated with HOV-189 (FIG. 11). Viral titers at the end of 2 weeks showed that the average titer of injected tumors was 3.37 x 10 ³ PFU per g tissue compared to the average of uninjected tumors, which was 1.15 x 10 ³ PFU per g tissue.

Review

Triple negative breast cancer (TNBC) accounts for 15-20% of all breast cancer diagnoses. It usually affects young women and tends to exhibit an aggressive biology with high relapse rates and poor overall survival. ^16,17 Unlike hormone receptor-positive diseases, TNBC lacks known biological markers for the development and administration of effective ^targeted therapies. Therefore, the focus of neoadjuvant and adjuvant therapy is on cytotoxic chemotherapy, which can be associated with many systemic side effects. ^{11 ,13}

In October 2015, the US Food and Drug Administration (FDA) designated herpes simplex as T-VEC (Talimogen laherparebvec) as the first oncolytic virus (OV) for use in humans. The virus (HSV-1) was approved. ¹⁸ This approval was a milestone in the fields of virology and immunotherapeutics, and sparked great interest in the further development of OVs for the treatment of other cancers, including TNBC. OVs show a natural affinity for cancer cells compared to normal cells, and preferentially infect cancer cells by taking advantage of pathological disorders in cancer cells, such as changes in intracellular signal transduction pathways and overexpression of cell surface receptors. ^{19 -21} In addition, when infected cells are destroyed mediated by OV, cytokines, tumor-associated antigens (TAAs), and damage-associated molecular pattern molecules (DAMPs) that stimulate both the innate and adaptive immune systems against cancer cells are released. associated molecular pattern molecules) and pathogen-associated molecular pattern (PAMP) molecules are released. ^20,22-26 TNBC exhibits ^increased genetic instability, increased numbers of neoantigens, and increased numbers of tumor infiltrating lymphocytes (TIL) in the microenvironment. ¹⁴ This makes TNBC more immunogenic than non-triple negative disease and an interesting candidate for OV induction therapy.

This study demonstrates that HOV-189, a novel chimeric parapoxvirus, has in vitro cytotoxic effects in four different TNBC cell lines of both metastatic and non-metastatic origin. A single intratumoral injection of HOV-189 in athymic nude mouse TNBC xenografts significantly reduced tumor size without significant signs of toxicity. Viruses were also detected in non-injected distant tumors in which tumor size was stabilized. Thus, HOV-189 shows the ability to translocate systemically and target distant disease sites, which can be applied to neoadjuvant therapy and metastatic settings.

Interestingly, an in vivo reduction in tumor size was observed with HOV-189 doses as low as 10 ³ PFU per tumor. This suggests that anti-tumor effects are unlikely to result from direct oncolysis due to viral replication, as HOV-189 exhibited poor in vitro replication. Genetic sequence analysis of HOV-189 shows that it is closely related to one of its parent viruses, parapoxvirus sheeppox virus (ORFV). Previous studies on ORFV showed that ORFV treatment induced potent immunomodulatory effects, especially with regard to the cellular activation of natural killer cells (NK). ^{27 ,28} Treatment of ultraviolet (UV) inactivated ORFV evoked a similar, albeit weaker, response, suggesting that the virus itself possesses antigenic structural components capable of eliciting an immune response unrelated to actual replication. show that there is Assuming that the gene sequence of HOV-189 is very closely related to the ORFV NZ2 virus, the applicant hypothesizes that the mechanism of anti-cancer action of HOV-189 is likely to be immune cell-mediated, possibly NK cell-mediated, which at low doses This explains the effect shown and its poor replication in vitro.

Compared to other OVs, ORFV has not been well studied with respect to clinical therapeutics development. Much of what is known about its natural history has been gleaned from veterinary medicine. However, there are several properties of ORFV that could be advantageous for development as an OV for the treatment of human cancer. First, ORVF infection does not cause serious disease in humans. ²⁹ Second, ORFV infection induces strong immune system stimulation (Th1-dominant) and even inactivated viral particles retain the ability to elicit an immune response. ^{30 , 31} Third, neutralizing antibodies are rare and reinfection may occur despite the production of antibodies against the ORF. This means that repeated administrations to the same patient may be possible, ²⁸ which is a logistical improvement for other OVs in clinical development that require a second dose of antigen-specific virus or serotyping for continued response. Finally, the clinical response using the low viral titer of ORFV is another substantial improvement for OV development since OV production is difficult, costly and time consuming and typically requires titers of 10 ⁶ to 10 ⁹ PFU per injection.

In summary, HOV-189 is a novel wild-type chimeric parapoxvirus that is effective against TNBC in vitro and in vivo. Targeted therapies for the treatment of TNBC are lacking, and HOV-189 represents a promising avenue for immunotherapeutic agents in this area. In view of future research directions, Applicants are planning further preclinical trials in other xenograft models as well as genetic modifications to wild viruses to improve tumor selectivity and overall efficacy.

<Table 4>

Example 5. Recombination chimera Production of poxvirus

#33 chimera Construction of a shuttle vector for insertion of a foreign gene expression cassette into the poxvirus genome

To construct the thymidine kinase ( TK ) shuttle vector, the left and right flank sequences of the TK gene of #33 chimeric poxvirus were mixed with Q5 High-Fidelity 2X Master Mix (New England Biolabs Inc). ., Ipswich, MA) and PCR amplification from #33 genomic DNA using the following primers :

The two fragments were ligated together using the gene splicing method by overlapping extension. ³² The resulting fragment was digested with NdeI and EcoRI and cloned into the same digested plasmid pGPT to obtain p33NC -TK . The flanking sequence of TK in the shuttle vector was confirmed by sequencing. p33NC-TK has left and right flanking sequences of TK separated by SacI, SalI, BamHI, NheI and NotI, and as a transient dominant selectable marker, Escherichia coli driven by the vaccinia virus (VACV) early promoter p7.5E. Contains the Escherichia coli guanine phosphoribosyltransferase (gpt) gene.

The F14.5L shuttle vector was constructed similarly. The left and right flanking sequences of the F14.5L gene of #33 chimeric poxvirus were PCR amplified from #33 genomic DNA using Q5 High-Fidelity 2X Master Mix (New England Biolabs Inc., Ipswich, Mass.) and the following primers: did:

The two fragments were ligated together using the gene splicing method by overlapping extension. The resulting fragment was digested with NdeI and EcoRI and cloned into the same digested plasmid pGPT to obtain p33NC -F14.5L . The flanking sequence of F14.5L in the shuttle vector was confirmed by sequencing. p33NC-F14.5L contains sequences flanking the left and right flanks of F14.5L separated by HindIII, SacI, XhoI, BamHI, NheI and NotI, and as a transient dominant selectable marker Escheri driven by the VACV early promoter p7.5E. contains the chia coli gpt gene.

#33 chimera Construction of Shuttle Vector for Fusion of Poxvirus Essential Genes and MicroRNA Target Sequences

Left and right sides of the D4R gene of #33 chimeric poxvirus to fuse the target sequence of miR-100 to the 3 ' end of uracil DNA glycosylase (encoded by gene D4R in vaccinia virus) of #33 chimeric poxvirus The flanking sequence was PCR amplified from #33 genomic DNA using Q5 High-Fidelity 2X Master Mix (New England Biolabs Inc., Ipswich, MA) and the following primers:

The two fragments were ligated together using the gene splicing method by overlapping extension. The resulting fragment was digested with NdeI and EcoRI and cloned into the same digested plasmid pGPT to p33NCD4R - miR100t. and p33NCD4R - miR100t -2 was obtained. The flanking sequence of D4R in the shuttle vector was confirmed by sequencing. As expected, p33NCD4R-miR100t It contains 4 copies of the miR-100 target sequence fused to the 3'-end of D4R , while p33NCD4R-miR100t-2 is a spontaneous mutant in which 2 copies of the miR-100 target sequence are deleted. Both vectors contain Escherichia coli gpt driven by the VACV early promoter p7.5E as a transiently dominant selectable marker.

To fuse the target sequence of Let-7c to the 3' end of uracil DNA glycosylase (encoded by gene D4R in vaccinia virus) of #33 chimeric poxvirus, the left and right sides of the D4R gene of #33 chimeric poxvirus The right flanking sequence was PCR amplified from #33 genomic DNA using Q5 High-Fidelity 2X Master Mix (New England Biolabs Inc., Ipswich, MA) and the following primers:

The two fragments were ligated together using the gene splicing method by overlapping extension. The resulting fragment was digested with NdeI and EcoRI and cloned into the same digested plasmid pGPT to obtain p33NCD4R - Let7ct . The flanking sequence of D4R in the shuttle vector was confirmed by sequencing. p33NCD4R-Let7ct as expected It contains 4 copies of the Let-7c target sequence fused to the 3'-end of D4R . It contains Escherichia coli gpt driven by the VACV early promoter p7.5E as a transiently dominant selectable marker.

To fuse the target sequence of miR-100 to the 3' end of the DNA polymerase of #33 chimeric poxvirus (encoded by gene E9L in vaccinia virus), the left and right flanks of the E9L gene of #33 chimeric poxvirus The sequence was PCR amplified from #33 genomic DNA using Q5 High-Fidelity 2X Master Mix (New England Biolabs Inc., Ipswich, MA) and the following primers:

The two fragments were ligated together using the gene splicing method by overlapping extension. The resulting fragment was digested with NarI and MfeI and cloned into the plasmid pGPT digested with NarI and EcoRI to obtain p33NCE9L - miR100t . The flanking sequence of ELL in the shuttle vector was confirmed by sequencing. p33NCE9L-miR100t as expected It contains 4 copies of the miR-100 target sequence fused to the 3'-end of E9L . It also contains Escherichia coli gpt driven by the VACV early promoter p7.5E as a transiently dominant selectable marker.

To fuse the target sequence of Let-7c to the 3' end of the DNA polymerase of #33 chimeric poxvirus (encoded by gene E9L in vaccinia virus), the left and right flanks of the E9L gene of #33 chimeric poxvirus The sequence was PCR amplified from #33 genomic DNA using Q5 High-Fidelity 2X Master Mix (New England Biolabs Inc., Ipswich, MA) and the following primers:

The two fragments were ligated together using the gene splicing method by overlapping extension. The resulting fragment was digested with NarI and MfeI and cloned into the plasmid pGPT digested with NarI and EcoRI to obtain p33NCE9L - Let7ct . The flanking sequence of E9L in the shuttle vector was confirmed by sequencing. p33NCE9L-Let7ct as expected It contains 4 copies of the Let-7c target sequence fused to the 3'-end of E9L . It also contains Escherichia coli gpt driven by the VACV early promoter p7.5E as a transiently dominant selectable marker.

Insertion of foreign gene expression cassettes into TK and F14.5L shuttle vectors

Human sodium iodine cotransporter (hNIS) expression cassette. The hNIS expression cassette with the VACV synthetic early promoter (SE) was PCR amplified using Q5 High-Fidelity 2X Master Mix (New England Biolabs Inc., Ipswich, Mass.) and the following primers:

The PCR fragment was digested with SacI and BamHI and cloned into the same digested plasmid p33NC-TK to obtain p33NCTK -SE- hNIS . The sequence of the hNIS expression cassette was confirmed by sequencing.

Emerald (a variant of GFP) expression cassette. The Emerald expression cassette with the VACV H5 early/late promoter was PCR amplified using Q5 High-Fidelity 2X Master Mix (New England Biolabs Inc., Ipswich, Mass.) and the following primers:

The PCR fragment was digested with SacI and BamHI and cloned into the same digested plasmid p33NC-TK to obtain p33NCTK -H5-Emerald . Emerald's sequence was confirmed by sequencing.

Firefly luciferase expression cassette. The firefly luciferase expression cassette with the VACV 11K late promoter was plasmid pCDNA3.1 (+)/Luc2=tdT ( PCR amplification from Addgene, Cambridge, MA):

The PCR fragment was digested with SacI and BamHI and cloned into the same digested plasmid p33NC-TK to obtain p33NCTK -11K- Fluc2 . The sequence of the firefly luciferase expression cassette was confirmed by sequencing. To generate a plasmid containing the firefly luciferase expression cassette with VACV SE and the H5 promoter, firefly luciferase cDNA was mixed with Q5 High-Fidelity 2X Master Mix (New England Biolabs Inc., Ipswich, MA) and the following primers. PCR amplification was performed from plasmid pCDNA3.1 (+)/Luc2=tdT (Addgene, Cambridge, MA) using:

The PCR fragment was digested with SacI and BamHI and cloned into the same digested plasmids p33NCTK-SE-hNIS and p33NCTK-H5-Emerald by replacing hNIS and emerald to obtain p33NCTK -SE-Fluc2 and p33NCTK -H5- Fluc2 , respectively. The sequence of the firefly luciferase cDNA in both vectors was confirmed by sequencing.

Emcheri expression cassette. MCherry cDNA was PCR amplified from the plasmid pLV-mCherry (Addgene, Cambridge, MA) using Q5 High-Fidelity 2X Master Mix (New England Biolabs Inc., Ipswich, MA) and the following primers:

The PCR fragment was digested with SacI and BamHI and cloned into the same digested plasmids p33NCTK-H5-Emerald and p33NCTK-11K-Fluc2 by substituting emerald and firefly luciferase for p33NCTK -H5- mCherry and p33NCTK -11K- mCherry was obtained respectively. The sequence of the m.cheri cDNA in both vectors was confirmed by sequencing.

Anti-PD-L1 single chain antibody expression cassette. Expression of an anti-PD-L1 single chain antibody comprising a VACV H5 promoter, an Igκ light chain leader sequence, V _H and V _L chain sequences of atezolizumab separated by a (G4S)3) linker sequence, and a C-terminal FLAG tag sequence. The cassette was synthesized by Integrated DNA Technologies (Coral, Iowa). The fragment was digested with HindIII and BamHI and cloned into the same digested plasmid p33NC-F14.5L to obtain p33NCF14.5L -J5-anti-PD-L1 . The sequence of the anti-PD-L1 single chain antibody expression cassette was confirmed by sequencing.

recombination chimera Production of poxvirus

After infecting CV-1 cells with parental virus at a multiplicity of infection (MOI) of 0.1 for 1 hour, transfer vectors ( Table 5) was transfected. Two days after infection, infected/transfected cells were harvested and recombinant virus was selected and plaques purified as previously described. ³³

<Table 5>

Example 6. chimera Poxvirus compositions and uses thereof

Applicants recently developed novel oncolytic chimeric poxviruses using a unique methodology for viral chimera generation, followed by high-throughput screening in NCI-60 cell line and pancreatic cell line. This novel chimeric poxvirus exploits the best targeting potential of several parental viruses and exhibits superior tumor killing effects in more than 70 cancer cell lines compared to their parental viruses and oncolytic viruses currently in human clinical trials. In human triple negative breast cancer, pancreatic cancer and lung cancer xenograft models, the novel chimeric poxvirus can shrink tumors with a single intratumoral injection of virus as low as 1000 plaque forming units without apparent side effects. This is 2 to 5 logs lower than most oncolytic viruses in clinical trials. In addition, the chimeric poxvirus effectively spreads from injected tumors to uninjected tumors, resulting in a large abscopal effect (shrinking of distant uninjected tumors).

To help monitor viral infection and replication in vitro and in vivo, emerald (GFP variant), emcheri (red fluorescent protein) and firefly luciferase expression cassettes were inserted into chimeric poxviruses. The expression of these optical imaging genes is readily detectable, greatly helping to monitor viral replication and spread in vivo without significantly affecting viral replication and potency.

Arming oncolytic viruses with therapeutic genes is a widely accepted strategy to improve the antitumor efficacy of oncolytic viruses. Of all the therapeutic genes tested, the human sodium iodine cotransporter (hNIS) has shown great promise in both preclinical and clinical studies. hNIS is a membrane-bound glycoprotein present on the basolateral surface of thyroid follicular cells. It transports iodine to the cytosol where it is organized during thyroid hormone synthesis. This molecule has been successfully used to accumulate radioiodine for both imaging and treatment of differentiated thyroid cancer, resulting in high response and cure rates (>90%). The hNIS expression cassette is expected to be inserted into chimeric poxviruses to convert non-thyroid carcinomas into “thyroid-like” cancers and respond to radioiodine or rhenium 188 therapy. Thus, non-thyroid carcinomas can be imaged using radioactive iodine after conversion to "thyroid-like" cancers, possibly through at least three mechanisms: intrinsic oncolytic activity of oncolytic viruses, targeted radiation therapy, and oncolytic viruses and It will be destroyed by the anti-tumor immune response mediated by radiation therapy. Applicants have shown that hNIS is properly expressed on the cell membrane of tumor cells after infection with an hNIS-expressing chimeric poxvirus. Additionally, initial experimental results indicate that insertion of the hNIS expression cassette does not affect the intrinsic oncolytic activity of the parental virus both in vitro and in animal models. In addition, Applicants have shown that hNIS expressing chimeric poxviruses are safe in tumor-bearing mice.

Immune checkpoint inhibitors represent breakthrough drugs in the treatment of solid tumors and have been approved for the treatment of melanoma, non-small cell lung carcinoma and renal cell carcinoma. These drugs require a pre-existing antitumor immune response. The priming of the immune system by oncolytic viruses sensitizes the patient's immune repertoire, which will further benefit anti-PD-1/PD-L1 and anti-CTLA-4 therapies. Co-administration of oncolytic viruses with immune checkpoint inhibitors can overcome several immune pathways that induce immune tolerance. In addition, oncolytic viruses promote the infiltration of cytotoxic CD8 T cells into infected tumors and induce upregulation of CTLA-4 or PD-L1 through the activation of IFN-γ-producing cytotoxic CD8 T cells, resulting in anti-CTLA-4 and antibody-PD-1/PD-L1 therapy to reach maximum therapeutic potential. Data from several preclinical studies support the combination of oncolytic viral therapy and checkpoint blockade. A clinical trial evaluating the first FDA-approved combination of oncolytic virus T-VEC with anti-CTLA-4 and anti-PD-1 antibodies is ongoing. Initial results are encouraging. To enhance the antitumor immune response initiated by a chimeric poxvirus, in particular a chimeric poxvirus expressing hNIS, an anti-PD-L1 expression cassette will be inserted into the chimeric poxvirus or chimeric poxvirus expressing hNIS. Applicants believe that insertion of hNIS into an oncolytic virus will act synergistically on tumor cell killing with radioactive iodine and nuclear medicine imaging of infected tumor cells, and immune stimulatory transgenes such as anti-PD-L1 within the same vector. It is expected that the expression of <RTI ID=0.0>significantly</RTI> enhances the anti-tumor immune response while potentially reducing off-target autoimmune toxicity.

Example 7. Pancreatic cancer using oncolytic virus therapy targeting

Cytotoxicity assay

3×10 ³ cancer cells per well were plated for 24 hours in 100 μl RPMI 5% FBS, 1% antibiotic-antimycotic solution, and cancer cell lines Panc-1 (FIGS. 12A-12B), MiaPaCa-2 (FIGS. 12C-12D), BxPC- 3 (Figs. 12e-12f), SU.86.86 (Figs. 12g-12h), Capan-1 (Figs. 12i-12j), and AsPC-1 (Figs. 12k-12k). Then, 20 μl of virus of #33, OncoVEX ^GFP , GLV-1h68, or #189 was added at multiple infectivity (MOIs) of 1, 0.1, and 0.01. Cell viability assays were analyzed daily by adding 20 μl of CellTiter 96 Aquas One Solution Cell Proliferation Assay to all wells and taking colorimetric readings after 1 hour incubation. Experimental results were normalized to medium alone and MOI 0 control. This experiment was repeated in triplicate. Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point. For SU.86.86, statistical analysis was performed using an unpaired t-test at each MOI.

virus growth curve

Cancer cell lines Panc-1 (FIGS. 13A-13B), MiaPaCa-2 (FIGS. 13C-13D), BxPC were plated in triplicate for 24 hours at 5x10 ⁵ cells per well in 2mL RPMI 10% FBS, 1% antibiotic-antimycotic solution. Viral replication curves were performed on -3 (FIGS. 13E-13F), SU.86.86 (FIGS. 13G-13H), Capan-1 (FIGS. 13I-13J), and AsPC-1 (FIGS. 13K-13L). The medium was then aspirated and #33, OncoVEX ^GFP , OncoVEXGFP, GLV-1h68 or #189 was shaken every 20 minutes at a multiplicity of infection degree (MOI) of 0.01 in 500 μl of RPMI 2.5% FBS, 1% antibiotic-antimycotic solution. was added for 1 hour. At 1 hour, the medium was aspirated and 1.5 mL of RPMI 2.5% FBS, 1% antibiotic-antimycotic solution was added. At 24, 48, and 72 hours, cells and supernatant were collected, and after three freeze-thaw cycles, serial dilutions were performed in duplicate. This experiment was repeated in duplicate. Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point.

Treatment of pancreatic cancer tumors in vivo

Eighteen athymic Nude- Foxn1 ^nu female nude mice (Envigo, Indianapolis, IN) were implanted with 2x10 ⁶ MiaPaCa-2 per flank tumor. When the tumor size reached 400 mm ³ , 50 μl of PBS (3 mice), #33 (5 mice), #33-(SE)hNIS or #33-(SE)hNIS-E9LmiR100t (5 mice) was administered to the left tumor. were injected at approximately 1x10 ⁵ PFU per dose. The actual dose of HOV-33 was 7.8x10 ⁴ . The dose of HOV-33-SE/hNIS was 4.5x10 ⁴ . The actual dose of HOV-33-SE/hNIS-E9L-miR100t was 1.6x10 ⁵ . Net weight change and rate of change of injected and non-injected tumors were recorded twice weekly for 43 days (FIG. 14A-FIG. 14C). All mice were sacrificed on day 43 and viral titers were measured in the mouse organs. Significant in injected tumors when comparing #33, #33-(SE)hNIS, and #33-(SE)hNIS-E9LmiR100t (FIG. 14B, p = 0.01, p = 0.01 and p=0.0001, respectively) to the PBS control group. A difference appeared. A significant difference appeared only in the non-injected tumor group between the PBS control group and #33-(SE)hNIS (FIG. 14C; p = 0.03).

Twenty-six athymic Nude- Foxn1 ^nu female nude mice (Envigo, Indianapolis, IN) were implanted with 1.25x10 ⁶ Panc-1 per flank tumor. When the tumor size reached approximately 250 mm ³ , 50 μl of PBS (4 mice), #33 (6 mice), #33-(SE)hNIS (6 mice), #33-(SE)hNIS-E9LmiR100t ( 5) or #33-(H5)Fluc2 at approximately 1x10 ³ PFU per dose. The actual dose of HOV-33 was 8.6x10 ² . The actual dose of HOV-33-SE/hNIS was 6.3x10 ² . The actual dose of HOV-33-H5Fluc was 1x10 ⁴ . The actual dose of HOV-33-SE/hNIS-E9L-miR100t was 1.0x10 ³ . Net weight change and percent change in injected and non-injected tumors were recorded twice weekly for 43 days ( FIGS. 15A-15C ). All mice were sacrificed on day 45. There was a significant difference in the rate of change in the volume of injected tumors in all groups compared to the PBS control group (FIG. 15B; p=0.0001). in uninjected tumors when comparing #33, #33-(H5)Fluc2, and #33-(SE)hNIS-E9LmiR100t (FIG. 15C; p = 0.003, p = 0.008, p=0.002, respectively) with the PBS control. A significant difference was found.

Twice a week, one PBS control mouse and three #33-(H5)Fluc2 injected mice were intraperitoneally injected with 4.28 mg of luciferin in 150 μl of PBS. After 7 minutes, luciferase images were obtained at standard exposures. Relative units at each time point were recorded and analyzed relative to PBS control mice as background (FIG. 16).

Example 8. Colon cancer using oncolytic virus therapy targeting

Cytotoxicity assay

HT-29 (FIGS. 17A-17B) and HCT-116 (FIGS. 17C-17D) cancer cell lines by plating 3x10 ³ cells per well in 100 μl McCoy's 5A medium, 5% FBS, 1% antibiotic-antimycotic solution for 24 hours. A cytotoxicity assay was performed. Then, 20 μl of virus of #33, OncoVEX ^GFP , GLV-1h68, or #189 was added at multiple infectivity (MOIs) of 1, 0.1, and 0.01. Daily cell viability assays were performed by adding 20 μl of CellTiter 96 Aquas One Solution Cell Proliferation Assay to all wells and taking colorimetric readings after 1 hour incubation. Experimental results were normalized to medium alone and MOI 0 control. This experiment was repeated in triplicate. Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point.

SW620 (FIGS. 18A-18B), SW480 (FIGS. 18C-18D), and COLO 320DM (FIG ^. 18E- f) A cytotoxicity assay was performed in cancer cell lines. Then, 20 μl of virus of #33, OncoVEX ^GFP , GLV-1h68, or #189 was added at multiple infectivity (MOIs) of 1, 0.1, and 0.01. Daily cell viability assays were performed by adding 20 μl of CellTiter 96 Aquas One Solution Cell Proliferation Assay to all wells and taking colorimetric readings after 1 hour incubation. Experimental results were normalized to medium alone and MOI 0 control. This experiment was repeated in triplicate. Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point.

Cytotoxicity assay was performed in LoVo (FIG. 19A-19B) cancer cell line by plating 3×10 ³ cells per well in 100 μl F-12K medium, 5% FBS, 1% antibiotic-antimycotic solution for 24 hours. Then, 20 μl of virus of #33, OncoVEX ^GFP , GLV-1h68, or #189 was added at multiple infectivity (MOIs) of 1, 0.1, and 0.01. Daily cell viability assays were performed by adding 20 μl of CellTiter 96 Aquas One Solution Cell Proliferation Assay to all wells and taking colorimetric readings after 1 hour incubation. Experimental results were normalized to medium alone and MOI 0 control. This experiment was repeated in triplicate. Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point.

virus growth curve

HT-29 (FIGS. 20A-20B) and HCT-116 (FIGS. 20C-20D) cancer cells were plated in triplicate for 24 hours at 5x10 ⁵ cells per well in 2 mL McCoy's 5A medium, 10% FBS, 1% antibiotic-antimycotic solution. Viral replication curves were performed on the cell lines. The medium was then aspirated and #33, #33-(SE)hNIS, #33-(H5)Emerald, OncoVEX ^GFP , GLV-1h68, or #189 was added to 500 μl of McCoy 5A medium 2.5% FBS, 1% A multiplicity of infection degree (MOI) of 0.01 in an antibiotic-antimycotic solution was added for 1 hour with shaking every 20 minutes. At 1 hour, the medium was aspirated and 1.5 mL of McCoy's 5A medium 2.5% FBS, 1% antibiotic-antimycotic solution was added. At 24, 48, and 72 hours, cells and supernatant were collected, and after three freeze-thaw cycles, serial dilutions were performed in duplicate. This experiment was repeated in duplicate. Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point.

Viral replication curves were performed in SW620 (FIGS. 21A-21B) and SW480 (FIGS. 21C-21D) cancer cell lines by plating 5x10 ⁵ cells per well in triplicate for 24 hours in 2 mL RPMI 10% FBS, 1% antibiotic-antimycotic solution. did The medium was then aspirated and #33, #33-(SE)hNIS, #33-(H5)Emerald, OncoVEX ^GFP , GLV-1h68, or #189 was added to 500 μl of RPMI 2.5% FBS, 1% antibiotic- In antifungal solution, a multiplicity of infection degree (MOI) of 0.01 was added for 1 hour with shaking every 20 minutes. At 1 hour, the medium was aspirated and 1.5 mL of RPMI 2.5% FBS, 1% antibiotic-antimycotic solution was added. At 24, 48, and 72 hours, cells and supernatant were collected, and after three freeze-thaw cycles, serial dilutions were performed in duplicate. This experiment was repeated in duplicate. Statistical analysis was performed comparing #33 to the other experimental groups using one-way ANOVA at each time point.

HCT-116 #33-(SE) hNIS immunohistochemistry

In vitro imaging of #33-(SE)hNIS was performed in HCT-116 at 24, 48 and 72 hours with MOIs of 1, 0.1 and 0.01. 2 x 10 ⁵ HCT 116 cells were added to each well of an 8 chamber slide in 500 μl of 10% FBS McCoy 5A medium. After 24 hour incubation the medium was aspirated and the appropriate MOI of #33-(SE)hNIS was added to each well in 200 μl of 2.5% FBS McCoy 5A medium. After 1 hour, the medium was aspirated and the cells were washed twice with PBS. The medium was replaced with 1 mL 10% FBS McCoy 5A medium. After 24, 48 or 72 hours, the medium was aspirated. Fixation was performed for 15 min at room temperature with 4% paraformaldehyde. Then it was washed twice with PBS. Permeabilization was performed on ice with 0.1% Triton X-100 in PBS for 5 minutes. Cells were washed again with PBS. The slides were then incubated in TNB blocking buffer (TNB blocking buffer: 0.1M Tris-HCl, PH7.5, 0.15 NaCl and 0.5% blocking reagent-Perkin Elmer, cat FP1020) at 37°C for 30 min. . A 1:50 dilution of mouse anti-human sodium iodine transporter (hNIS) antibody (ab 17795) in TNB blocking buffer was added and incubated overnight at 4°C. The slides were then washed twice with PBS before the addition of a 1:100 dilution of goat anti-mouse IgG H & L (Alexa Fluor 488) (ab150113) in TNB blocking buffer for 1 hour at room temperature. Incubated. Then, the cells were washed twice with PBS. A 1:200 dilution of rabbit anti-vaccinia (ab35219) in TNB was added and incubated overnight at 4°C. Then, the cells were washed twice with PBS. Blocked with TNB for 30 minutes. Next, a 1:100 dilution of goat anti-rabbit secondary antibody was added and left at room temperature for 1 hour. After washing twice with PBS, a 1:1000 dilution of DAPI was added for 5 minutes at room temperature. Again, a PBS wash was performed. Images were taken using the EVOS automated cell imaging system (FIG. 22).

HT-29 #33-(SE) hNIS immunohistochemistry

In vitro imaging of #33-(SE)hNIS was performed in HCT-29 at 24, 48 and 72 hours with MOIs of 1, 0.1 and 0.01. 2 x 10 ⁵ HCT 116 cells were added to each well of an 8 chamber slide in 500 μl of 10% FBS McCoy 5A medium. After 24 hour incubation the medium was aspirated and the appropriate MOI of #33-(SE)hNIS was added to each well in 200 μl of 2.5% FBS McCoy 5A medium. After 1 hour, the medium was aspirated and the cells were washed twice with PBS. The medium was replaced with 1 mL 10% FBS McCoy 5A medium. After 24, 48 or 72 hours, the medium was aspirated. Fixation was performed for 15 min at room temperature with 4% paraformaldehyde. Then it was washed twice with PBS. Permeabilization was performed with 0.1% Triton X-100 in PBS for 5 minutes on ice. Cells were washed again with PBS. The slides were then incubated in TNB blocking buffer (TNB blocking buffer: 0.1M Tris-HCl, PH7.5, 0.15 NaCl and 0.5% blocking reagent-PerkinElmer, cat FP1020) at 37°C for 30 minutes. A 1:50 dilution of mouse anti-human sodium iodine transporter (hNIS) antibody (ab 17795) in TNB blocking buffer was added and incubated overnight at 4°C. The slides were then washed twice with PBS before the addition of a 1:100 dilution of goat anti-mouse IgG H & L (Alexa Fluor 488) (ab150113) in TNB blocking buffer for 1 hour at room temperature. Incubated. Cells were then washed twice with PBS before adding a 1:200 dilution of rabbit anti-vaccinia (ab35219) in TNB and incubating overnight at 4°C. Cells were then washed twice with PBS. Blocked with TNB for 30 minutes. Next, a 1:100 dilution of goat anti-rabbit secondary antibody was added and left at room temperature for 1 hour. After washing twice with PBS, a 1:1000 dilution of DAPI was added for 5 minutes at room temperature. Again, a PBS wash was performed. Images were taken using the EVOS automated cell imaging system (FIG. 23).

Treatment of colorectal cancer tumors in vivo

Fourteen athymic Nude- Foxn1 ^nu female nude mice (Envigo, Indianapolis, IN) were implanted with 5x10 ⁶ cells of HT-29 per flank tumor. When tumor size reaches approximately 200 mm ³ , both tumors are injected with approximately 1x10 ⁵ PFU per dose of 50 μl of PBS (4 mice), #33 (5 mice), or #33-(H5)Fluc2 (5 mice). did Net weight change and rate of change of tumors were recorded twice weekly for 42 days. After 10 days, 2 mice from each group were sacrificed and viral titers and IHC were performed in the organs. All remaining mice were sacrificed on day 42 and viral titers were measured in the mouse organs. Significant differences were found in the rate of change in tumor volume when the PBS control group was compared to #33 (three mice) and #33-(H5)Fluc2 (p = 0.02 and p = 0.03, respectively) (FIG. 24).

Twice a week, one PBS control mouse and three #33-(H5)Fluc2 injected mice were intraperitoneally injected with 4.28 mg of luciferin in 150 μl of PBS. After 7 minutes, luciferase images were obtained at standard exposures. Relative units at each time point were recorded and analyzed relative to PBS control mice as background (FIG. 25).

Nineteen athymic Nude- Foxn1 ^nu female nude mice (Envigo, Indianapolis, IN) were injected with 5x10 ⁶ cells per flank tumor. HCT-116 was implanted. When the tumor size reached approximately 200 mm ³ , 50 μl of PBS (2 mice), #33 (3 mice), #33-(SE)hNIS, or #33-(H5)Fluc2 was administered to both tumors approximately 1x10 per dose. Injected with ⁵ PFU. Net weight change and rate of change of tumors were recorded twice weekly for 42 days. After 10 days, 2 mice from each group were sacrificed and viral titers and IHC were performed in the organs. All remaining mice were sacrificed on day 42 and viral titers were measured in the mouse organs. Tumor volume when PBS control was compared to #33 (3 mice), #33-(SE)hNIS and #33-(H5)Fluc2 (FIG. 26; p = p=0.0002, p=0.0001 and dp=0.0002, respectively) Significant differences were found in the rate of change.

Twice a week, one PBS control mouse and three #33-(H5)Fluc2 injected mice were intraperitoneally injected with 4.28 mg of luciferin in 150 μl of PBS. After 7 minutes, luciferase images were obtained at standard exposures. Relative units at each time point were recorded and analyzed relative to PBS control mice as background (FIG. 27).

Example 9. Lung cancer using oncolytic virus therapy targeting

Cytotoxicity assay

Oncolytic virus-mediated cytotoxicity in lung cancer and lung fibroblasts 72 h after infection. 5000 cells of A549, H2199 or HF1 fibroblasts were plated in each well of a 96-well plate. The following day, cells were infected with different viruses at the specified multiplicity of infection (MOI: 0, 0.001, 0.01, 0.1, 1 MOI) or mock-infected. Viruses used were #33, #33-(H5)Emerald, #189, GLV-1h68 and OncoVEX ^GFP . Cell viability was determined 72 hours after infection using CellTiter 96 Aquas One Solution (Promega; Cat # G3581). The viability of infected cells A549 (FIG. 28A), H2199 (FIG. 28B) and HF1 fibroblasts (FIG. 28C) were calculated relative to the viability of mock-infected cells.

Treatment of lung cancer tumors in vivo

A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 3) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group. After sorting, 10 ³ plaque forming units (PFU) of #33-(H5)Emerald, GLV1h68 or OncoVEX ^GFP were injected intratumorally into only the right tumor of each mouse. All three viruses encode a green fluorescent protein (GFP) gene. Mice were imaged twice weekly for green fluorescence (excitation: 465 and emission: 530 nm) using small animal imaging equipment (LagoX imaging system) and images were processed with AMIview image processing software (FIG. 29).

mouse weight. A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 4 or 5) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group. After sorting, 10 ³ PFU of the specified virus (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM , #189, PBS control) was injected intratumorally into only the right tumor of each mouse, or #33-(H5)Emerald was injected intraperitoneally (ip). Mice were weighed twice weekly and their rate of change in body weight was determined (FIG. 30). In [FIG. 30], each line represents the body weight of an individual mouse.

tumor regression . A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 4 or 5) to obtain similar mean tumor volumes (˜200 mm ³ ) in each group. After sorting, 10 ³ PFU of the specified virus (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM , #189, PBS control) was injected intratumorally into only the right tumor of each mouse, or #33-(H5)Emerald was injected intraperitoneally (ip). Twice weekly, both injected (FIG. 31A) and non-injected (FIG. 31B) tumor volumes were measured using a digital caliper (volume = {(length) ² x (width)/2}). In Figures 31A and 31B, each line represents the tumor volume of an individual mouse.

Volume of virus-injected tumors in the A549 xenograft model . A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 4 or 5) to obtain similar mean tumor volumes (˜200 mm ³ ) in each group. After sorting, 10 ³ PFU of the specified virus (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM , #189, PBS control) was injected intratumorally into only the right tumor of each mouse, or #33-(H5)Emerald was injected intraperitoneally (ip). Tumor volume was measured using a digital caliper twice weekly (volume = {(length) ² x (width)/2}). In FIG. 32 , each line represents the mean volume of injected tumors over time in an individual treatment group with standard deviation. Statistical Analysis: One-way ANOVA at Day 24 (* = p <0.05).

Volume of virus- free tumors in the A549 xenograft model . A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 4 or 5) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group. After sorting, 10 ³ PFU of the specified virus (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM , #189, PBS control) was injected intratumorally into only the right tumor of each mouse, or #33-(H5)Emerald was injected intraperitoneally (ip). Tumor volume was measured using a digital caliper twice weekly (volume = {(length) ² x (width)/2}). In FIG. 33 , each line represents the average volume of uninjected tumors over time in an individual treatment group with standard deviation. Statistical Analysis: One-way ANOVA at Day 24 (* = p <0.05).

Fold change in injected and non-injected tumor volume . A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 4 or 5) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group. After sorting, 10 ³ PFU of the specified virus (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM , #189, PBS control) was injected intratumorally into only the right tumor of each mouse, or #33-(H5)Emerald was injected intraperitoneally (ip). Tumor volume was measured using a digital caliper twice weekly (volume = {(length) ² x (width)/2}). The fold change in tumor volume was calculated by normalizing the tumor volume at different time points to the tumor volume at the time of virus injection (i.e., day 0). Each line represents the mean fold change in tumor volume in injected (FIG. 34A) and non-injected (FIG. 34B) tumors with standard deviation for an individual treatment group. Statistical Analysis: One-way ANOVA at Day 24 (* = p <0.05).

Biodistribution of Virus in Injected and Uninjected Tumors (A549 Model). A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 3) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group. After sorting, 10 ³ PFU of the indicated virus (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM ) was injected intratumorally into only the right tumor of each mouse. Six days after viral injection, tumors and normal organs were harvested. The harvested tissue was weighed, minced into small pieces and homogenized in 1 ml PBS using a Bullet Blender Gold homogenizer. The homogenates were subjected to 3 freeze-thaw cycles followed by 1 minute sonication. The homogenate was spun down at 1000 rpm for 3 minutes and the supernatant was collected. Supernatants were serially diluted and viral titers were determined using a standard plaque assay. [FIG. 35A] shows the virus titer for tumors injected with each virus in PFU per gram of tumor, and [FIG. 35B] shows the virus titer for tumors not injected with each virus in PFU per gram of tumor.

Virus titers in mouse ovaries (A549 model). A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 3) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group. After sorting, 10 ³ PFU of the indicated virus (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM ) was injected intratumorally into only the right tumor of each mouse. Six days after viral injection, tumors and normal organs were harvested. The harvested tissue was weighed, minced into small pieces and homogenized in 1 ml PBS using a Bullet Blender Gold homogenizer. The homogenates were subjected to 3 freeze-thaw cycles followed by 1 minute sonication. The homogenate was spun down at 1000 rpm for 3 minutes and the supernatant was collected. Supernatants were serially diluted and viral titers were determined using a standard plaque assay. [Fig. 36] shows the virus titer for each virus as PFU per gram of tissue (ovary).

Virus titer in blood 20 days after virus injection . A549 human lung cancer cells were cultured, trypsinized, washed with PBS, and resuspended in 1:1 PBS-Matrigel to obtain 5x10 ⁶ cells per 100 μl. 100 μl of the cell suspension was injected subcutaneously into each side of the upper flank of athymic nude mice to generate 2 tumors per mouse. Three weeks after tumor cell injection, mice were grouped into different treatment groups (n = 3) to obtain similar average tumor volumes (~ 200 mm ³ ) in each group. After sorting, 10 ³ PFU of the indicated virus (#33, #33-(H5)Emerald, GLV-1h68, OncoVEX ^GFP , T-VEC ^TM ) was injected intratumorally into only the right tumor of each mouse. Blood was collected from mice (n = 3) via facial vein puncture. After three freeze-thaw cycles, blood was serially diluted and viral titers were determined using a standard plaque assay (FIG. 37). ** ND means no virus was detected.

references

P embodiment

Embodiment P1. A chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, wherein the nucleic acid sequence comprises vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus Consisting of strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ledle-Panthox, vaccinia virus strain AS, sheeppox virus strain NZ2 and pseudopox virus strain TJS. A chimeric poxvirus comprising nucleic acid fragments from two or more poxvirus strains selected from the group.

Embodiment P2. The chimeric poxvirus of embodiment P1, wherein said nucleic acid sequence has at least 80% sequence identity.

Embodiment P3. The chimeric poxvirus of embodiment P1 or P2, wherein said nucleic acid sequence has at least 85% sequence identity.

Embodiment P4. The chimeric poxvirus of any one of embodiments P1 to P3, wherein said nucleic acid sequences have at least 90% sequence identity.

Embodiment P5. The chimeric poxvirus of any one of embodiments P1 to P4, wherein said nucleic acid sequences have at least 95% sequence identity.

Embodiment P6. The chimeric poxvirus of any one of embodiments P1 to P5, wherein said nucleic acid sequences have at least 98% sequence identity.

Embodiment P7. The method of any one of embodiments P1 to P6, wherein said nucleic acid fragment is vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus A chimeric poxvirus derived from strain Elstri, vaccinia virus strain CL, vaccinia virus strain Ledle-Elora and vaccinia virus strain AS.

Embodiment P8. A chimeric poxvirus according to any one of embodiments P1 to P6, wherein said nucleic acid fragments are from sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS.

Embodiment P9. The method of embodiment P1, wherein the chimeric poxvirus is

(i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, harepox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia virus strain Radle Infecting the cells with two or more poxvirus strains selected from the group consisting of Les-Panthox, vaccinia virus strain AS, sheeppox virus strain NZ2, and pseudovaxpox virus strain TJS; and (ii) allowing the two or more poxvirus strains to replicate to form a chimeric poxvirus.

Embodiment P10. The method of embodiment P9, wherein the cell is vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL , a chimeric poxvirus that is infected with the vaccinia virus strain Ledle-Elora and the vaccinia virus strain AS.

Embodiment P11. The chimeric poxvirus of embodiment P9, wherein the cell is infected with sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS.

Embodiment P12. The chimeric poxvirus of any one of embodiments P1 to P11, wherein said chimeric poxvirus is an oncolytic virus.

Embodiment P13. The chimeric poxvirus of any one of embodiments P1 to P12, wherein the poxvirus comprises a miRNA binding sequence.

Embodiment P14. The chimeric poxvirus of embodiment P13, wherein said miRNA binding sequence forms part of a DNA polymerase gene of said chimeric poxvirus.

Embodiment P15. An isolated nucleic acid encoding the chimeric poxvirus of any one of embodiments P1-P14.

Embodiment P16. A pharmaceutical composition comprising a therapeutically effective amount of any one of embodiments P1 to P14.

Embodiment P17. A method of treating cancer in a subject in need thereof, comprising the step of treating cancer in the subject by administering to the subject a therapeutically effective amount of a chimeric poxvirus of any one of embodiments P1 to P14. method.

Embodiment P18. The method according to embodiment P17, wherein said cancer is breast cancer, colon cancer, kidney cancer, leukemia, lung cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer, brain cancer, liver cancer, stomach cancer or sarcoma.

Embodiment P19. The method of embodiment P17 or P18, wherein said administering comprises administering a first chimeric poxvirus and a second chimeric poxvirus.

Embodiment P20. The method of embodiment P19, wherein said first chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity with SEQ ID NO: 1, said nucleic acid sequence comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht , comprising nucleic acid fragments from vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Radle-Elora and vaccinia virus strain AS method.

The method of embodiment P21, embodiment P19 or P20, wherein said second chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 2, wherein said nucleic acid sequence comprises sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS A method comprising a nucleic acid fragment from.

Embodiment P22. The method of any one of embodiments P19 to P21, wherein said first chimeric poxvirus and said second chimeric poxvirus are administered in a combined synergistic amount.

Embodiment P23. The method of any one of embodiments P19 to P22, wherein said first chimeric poxvirus and said second chimeric poxvirus are administered concurrently.

Embodiment P24. The method of any one of embodiments P19 to P22, wherein said first chimeric poxvirus and said second chimeric poxvirus are administered sequentially.

Embodiment P25. The method of any one of embodiments P19 to P24, wherein said poxvirus is administered at least 10 ⁴ plaque forming units (Pfu)/kg.

Embodiment P26. The method of any one of embodiments P19 to P25, wherein said poxvirus is administered at at least 10 ⁶ plaque forming units (Pfu)/kg.

Embodiment P27. The method of any one of embodiments P19 to P26, wherein said poxvirus is administered at about 10 ⁸ Plaque Forming Units (Pfu)/kg.

Embodiment P28. A method for forming a chimeric poxvirus comprising (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia Infecting the cell with two or more poxvirus strains selected from the group consisting of virus strain CL, vaccinia virus strain Leslie-Elemental, vaccinia virus strain AS, sheeppox virus strain NZ2, and pseudopox virus strain TJS; and (ii) allowing the two or more poxvirus strains to replicate to form the chimeric poxvirus.

Embodiment P29. The method of embodiment P28, wherein said two or more poxvirus strains are each present at a multiplicity of infection of less than about 1.

Embodiment P30. The method of embodiment P28 or P29, wherein the two or more poxvirus strains are each present at a multiplicity of infection of less than about 0.1.

Embodiment P31. The method of any one of embodiments P28 to P30, wherein said two or more poxvirus strains are each present at a multiplicity of infection of about 0.01.

Embodiment P32. The method of embodiment P28, wherein the cell is vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit pox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL , with vaccinia virus strain Ledle-Ilanto and vaccinia virus strain AS.

Embodiment P33. The method of embodiment P28, wherein said cells are infected with vaccinia virus strain NZ2 and pseudo vaccinia virus strain TJS.

Embodiment P34. The method of any one of embodiments P28 to P33, wherein said chimeric poxvirus is an oncolytic virus.

Embodiment P35. The method of any one of embodiments P28 to P34, wherein said chimeric poxvirus comprises a miRNA binding sequence.

Embodiment P36. A method of inhibiting cellular proliferation of a cell, comprising contacting the cell with the chimeric poxvirus of any one of embodiments P1 to P14.

Embodiment P37. The method of embodiment P36, wherein said cell is a cancer cell.

Embodiment P38. The method of embodiment P37, wherein the cancer cells are breast cancer cells, colon cancer cells, renal cancer cells, leukemia cells, lung cancer cells, melanoma cells, ovarian cancer cells, prostate cancer cells, pancreatic cancer cells, brain cancer cells, liver cancer cells, stomach cancer cells, or A method that is a sarcoma cell.

embodiment

Embodiment 1. A chimeric poxvirus comprising a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, wherein the nucleic acid sequence is (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbitpox Virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia virus strain Lederle-panel, vaccinia virus strain AS, sheeppox virus strain nucleic acid fragments from at least two poxvirus strains selected from the group consisting of NZ2 and pseudo vaccinia virus strain TJS; (ii) one or more anticancer nucleic acid sequences; or (iii) a chimeric poxvirus comprising a detectable moiety-encoding nucleic acid sequence.

The method of embodiment 2, embodiment 1, wherein the nucleic acid sequence is (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Nucleic acid fragments from at least two poxvirus strains selected from the group consisting of Elstree, vaccinia virus strain CL, vaccinia virus strain Ledle-Pelto, vaccinia virus strain AS, sheeppox virus strain NZ2, and pseudovax virus strain TJS. ; and (ii) one or more anti-cancer nucleic acid sequences.

Embodiment 3. The chimeric poxvirus of embodiment 1 or 2, wherein said one or more anti-cancer nucleic acid sequences form part of a non-essential gene of said chimeric poxvirus.

Embodiment 4. The chimeric poxvirus of embodiment 3, wherein said nonessential gene is a thymidine kinase gene.

Embodiment 5. The chimeric poxvirus of embodiment 3, wherein said nonessential gene is the F14.5L gene.

Embodiment 6. The chimeric poxvirus of any one of embodiments 1 to 5, wherein said one or more anti-cancer nucleic acid sequences independently encode a PD-L1 inhibitor or a sodium iodine cotransporter.

Embodiment 7. The chimeric poxvirus of embodiment 6, wherein said PD-L1 inhibitor is an anti-PD-L1 scFv.

Embodiment 8. The chimeric poxvirus of any one of embodiments 1 to 7, wherein some of said non-essential genes are deleted.

Embodiment 9. The chimeric poxvirus of any one of embodiments 1 to 8, wherein each of said one or more anti-cancer nucleic acid sequences is operably linked to a promoter.

Embodiment 10. The chimeric poxvirus of embodiment 9, wherein said promoter is the vaccinia virus early promoter.

Embodiment 11. The chimeric poxvirus according to embodiment 9 or 10, wherein said promoter is a synthetic early promoter.

Embodiment 12. The chimeric poxvirus of embodiment 9, wherein said promoter is a vaccinia virus late promoter.

Embodiment 13. The chimeric poxvirus according to embodiment 9 or 12, wherein said promoter is the H5 promoter or the 11K promoter.

Embodiment 14. The chimeric poxvirus of any one of embodiments 1 to 8, wherein said one or more anti-cancer nucleic acid sequences are operably linked to essential genes of said chimeric poxvirus.

Embodiment 15. The chimeric poxvirus of any one of embodiments 1 to 14, wherein said one or more anti-cancer nucleic acid sequences are operably linked to a DNA polymerase gene of said chimeric poxvirus.

Embodiment 16. The chimeric poxvirus of any one of embodiments 1 to 15, wherein said one or more anti-cancer nucleic acid sequences are operably linked to the 3' end of a DNA polymerase gene of said chimeric poxvirus.

Embodiment 17. The chimeric poxvirus of any one of embodiments 1 to 16, wherein said one or more anti-cancer nucleic acid sequences are operably linked to a uracil DNA glycosylase gene.

Embodiment 18. The chimeric poxvirus of any one of embodiments 1 to 17, wherein said one or more anti-cancer nucleic acid sequences are operably linked to the 3' end of a uracil DNA glycosylase gene.

Embodiment 19. The chimeric poxvirus of any one of embodiments 1 to 18, wherein said one or more anti-cancer nucleic acid sequences independently encode a miRNA binding sequence.

Embodiment 20. The chimeric poxvirus according to embodiment 19, wherein said miRNA binding sequence is a miR100 binding sequence or a let7c binding sequence.

Embodiment 21. The chimeric poxvirus of any one of embodiments 1 to 20, wherein said one or more anti-cancer nucleic acid sequences are a first anti-cancer nucleic acid sequence and a second anti-cancer nucleic acid sequence.

Embodiment 22. The chimeric poxvirus of embodiment 21, wherein said first anti-cancer nucleic acid sequence encodes a sodium iodine cotransporter and said second anti-cancer nucleic acid sequence encodes a miRNA binding sequence.

Embodiment 23. The chimeric poxvirus of embodiment 22, wherein said first anti-cancer nucleic acid sequence forms part of a thymidine kinase gene and said second anti-cancer nucleic acid sequence is operably linked to a uracil DNA glycosylase gene. .

Embodiment 24. The chimeric poxvirus of embodiment 22, wherein said first anti-cancer nucleic acid sequence forms part of a thymidine kinase gene and said second anti-cancer nucleic acid sequence is operably linked to a DNA polymerase gene.

Embodiment 25. The chimeric poxvirus of embodiment 21, wherein said first anti-cancer nucleic acid sequence encodes a sodium iodine cotransporter and said second anti-cancer nucleic acid sequence encodes a PD-L1 inhibitor.

Embodiment 26. The chimeric poxvirus of embodiment 25, wherein said first anti-cancer nucleic acid sequence forms part of a thymidine kinase gene and said second anti-cancer nucleic acid sequence forms part of a F14.5L gene.

Embodiment 27. The method of embodiment 1, wherein the nucleic acid sequence is (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Nucleic acid fragments from at least two poxvirus strains selected from the group consisting of Elstree, vaccinia virus strain CL, vaccinia virus strain Ledle-Pelto, vaccinia virus strain AS, sheeppox virus strain NZ2, and pseudovax virus strain TJS. ; and (ii) a chimeric poxvirus comprising said detectable moiety-encoding nucleic acid sequence.

Embodiment 28. The chimeric poxvirus of embodiment 27, wherein said nucleic acid sequence encoding a detectable moiety encodes a fluorescent moiety.

Embodiment 29. The chimeric poxvirus of embodiment 27 or 28, wherein said detectable moiety-encoding nucleic acid sequence forms part of a non-essential gene of said chimeric poxvirus.

Embodiment 30. The chimeric poxvirus of embodiment 29, wherein said non-essential gene is a thymidine kinase gene.

Embodiment 31. The chimeric poxvirus of embodiment 29 or 30, wherein some of said non-essential genes are deleted.

Embodiment 32. The chimeric poxvirus of any one of embodiments 27 to 31, wherein said detectable moiety encoding nucleic acid sequence is operably linked to a promoter.

Embodiment 33. The chimeric poxvirus of embodiment 32, wherein said promoter is the vaccinia virus early promoter.

Embodiment 34. The chimeric poxvirus of embodiment 33, wherein said promoter is a synthetic early promoter.

Embodiment 35. The chimeric poxvirus of embodiment 32, wherein said promoter is a vaccinia virus late promoter.

Embodiment 36. The chimeric poxvirus of embodiment 35, wherein said promoter is an H5 promoter or an 11K promoter.

Embodiment 37. The chimeric poxvirus of any one of embodiments 1 to 36, wherein said nucleic acid sequence has at least 80% sequence identity.

Embodiment 38. The chimeric poxvirus of any one of embodiments 1 to 37, wherein said nucleic acid sequence has at least 85% sequence identity.

Embodiment 39. The chimeric poxvirus of any one of embodiments 1 to 38, wherein said nucleic acid sequence has at least 90% sequence identity.

Embodiment 40. The chimeric poxvirus of any one of embodiments 1 to 39, wherein said nucleic acid sequence has at least 95% sequence identity.

Embodiment 41. The chimeric poxvirus of any one of embodiments 1 to 40, wherein said nucleic acid sequence has at least 98% sequence identity.

Embodiment 42. The method according to any one of embodiments 1 to 41, wherein the nucleic acid fragment is selected from vaccinia virus strain Brighton, raccoon fox virus strain Herman, harepox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD , a chimeric poxvirus derived from vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Radle-Pantylum and vaccinia virus strain AS.

Embodiment 43. A chimeric poxvirus according to any one of embodiments 1 to 41, wherein said nucleic acid fragment is derived from sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS.

Embodiment 44. The method according to any one of embodiments 1 to 43, wherein the chimeric poxvirus is (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, harepox virus strain Utrecht, vaccinia virus strain WR, vaccinia 2 selected from the group consisting of vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia virus strain Leslie-Elliotella, vaccinia virus strain AS, sheeppox virus strain NZ2 and pseudovax virus strain TJS Infecting cells with one or more poxvirus strains; and (ii) allowing the two or more poxvirus strains to replicate to form a chimeric poxvirus.

Embodiment 45. The method according to embodiment 44, wherein the cell is vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia A chimeric poxvirus that is infected with vaccinia virus strain CL, vaccinia virus strain Redle-Elora and vaccinia virus strain AS.

Embodiment 46. The chimeric poxvirus of embodiment 44, wherein said cell is infected with sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS.

Embodiment 47. The chimeric poxvirus of any one of embodiments 1 to 46, wherein said chimeric poxvirus is an oncolytic virus.

Embodiment 48. The chimeric poxvirus of any one of embodiments 1 to 47, wherein said poxvirus comprises a miRNA binding sequence.

Embodiment 49. The chimeric poxvirus of embodiment 48, wherein said miRNA binding sequence forms part of a DNA polymerase gene of said chimeric poxvirus.

Embodiment 50. An isolated nucleic acid encoding the chimeric poxvirus of any one of embodiments 1-49.

Embodiment 51. A pharmaceutical composition comprising a therapeutically effective amount of any one of embodiments 1 to 49.

Embodiment 52. A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a chimeric poxvirus of any one of embodiments 1 to 49, thereby treating the cancer in the subject. How to include steps.

Embodiment 53. The method of embodiment 52, wherein said cancer is breast cancer, colon cancer, kidney cancer, leukemia, lung cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer, brain cancer, liver cancer, stomach cancer or sarcoma.

Embodiment 54. The method of embodiment 52 or 53, wherein said cancer is triple negative breast cancer.

Embodiment 55. The method of any one of embodiments 52 to 54, wherein said administering comprises administering a first chimeric poxvirus and a second chimeric poxvirus.

Embodiment 56. The method of embodiment 55, wherein said first chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity with SEQ ID NO: 1, said nucleic acid sequence comprising vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit Nucleic acid fragments from pox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstri, vaccinia virus strain CL, vaccinia virus strain Lethle-Elemental and vaccinia virus strain AS How to include.

The method of embodiment 57, embodiment 55 or 56, wherein the second chimeric poxvirus comprises a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 2, wherein the nucleic acid sequence comprises sheep pox virus strain NZ2 and pseudo vaccinia virus strain TJS A method comprising a nucleic acid fragment from.

Embodiment 58. The method of any one of embodiments 55 to 57, wherein said first chimeric poxvirus and said second chimeric poxvirus are administered in a combined synergistic amount.

Embodiment 59. The method of any one of embodiments 55 to 58, wherein said first chimeric poxvirus and said second chimeric poxvirus are administered simultaneously.

Embodiment 60. The method of any one of embodiments 55 to 58, wherein said first chimeric poxvirus and said second chimeric poxvirus are administered sequentially.

Embodiment 61. The method of any one of embodiments 52 to 60, wherein said poxvirus is administered at at least 10 ³ plaque forming units (Pfu)/kg.

Embodiment 62. The method of any one of embodiments 52 to 61, wherein said poxvirus is administered at about 10 ³ Plaque Forming Units (Pfu)/kg.

Embodiment 63. The method of any one of embodiments 51 to 61, wherein said poxvirus is administered at at least 10 ⁴ plaque forming units (Pfu)/kg.

Embodiment 64. The method of any one of embodiments 52 to 61, wherein said poxvirus is administered at about 4 x 10 ⁴ plaque forming units (Pfu)/kg.

Embodiment 65. The method of any one of embodiments 52 to 61, wherein said poxvirus is administered at about 5 x 10 ⁴ plaque forming units (Pfu)/kg.

Embodiment 66. The method of any one of embodiments 52 to 61, wherein said poxvirus is administered at at least 10 ⁶ plaque forming units (Pfu)/kg.

Embodiment 67. The method of any one of embodiments 52 to 61, wherein said poxvirus is administered at about 10 ⁸ Plaque Forming Units (Pfu)/kg.

Embodiment 68. A method of forming a chimeric poxvirus comprising: (i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, harepox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Els Infecting a cell with two or more poxvirus strains selected from the group consisting of tree, vaccinia virus strain CL, vaccinia virus strain Ledle-Elemental, vaccinia virus strain AS, sheeppox virus strain NZ2 and pseudovax virus strain TJS step; and (ii) allowing the two or more poxvirus strains to replicate to form the chimeric poxvirus.

Embodiment 69. The method of embodiment 68, wherein said two or more poxvirus strains are each present at a multiplicity of infection of less than about 1.

Embodiment 70. The method of embodiment 68 or 69, wherein said two or more poxvirus strains are each present at a multiplicity of infection of less than about 0.1.

Embodiment 71. The method of any one of embodiments 68 to 70, wherein said two or more poxvirus strains are each present at a multiplicity of infection of about 0.01.

Embodiment 72. The method according to embodiment 68, wherein the cell is vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia and with vaccinia virus strain CL, vaccinia virus strain Ledle-Ilanto, and vaccinia virus strain AS.

Embodiment 73. The method of embodiment 68, wherein said cells are infected with vaccinia virus strain NZ2 and pseudo vaccinia virus strain TJS.

Embodiment 74 The method of any one of embodiments 68 to 73, wherein said chimeric poxvirus is an oncolytic virus.

Embodiment 75. The method of any one of embodiments 68 to 74, wherein the virus comprises a miRNA binding sequence.

Embodiment 76. A method of inhibiting cellular proliferation of a cell, comprising contacting the cell with the chimeric poxvirus of any one of embodiments 1-49.

Embodiment 77. The method of embodiment 76, wherein said cell is a cancer cell.

Embodiment 78. The method according to embodiment 77, wherein the cancer cells are breast cancer cells, colon cancer cells, renal cancer cells, leukemia cells, lung cancer cells, melanoma cells, ovarian cancer cells, prostate cancer cells, pancreatic cancer cells, brain cancer cells, liver cancer cells , gastric cancer cells or sarcoma cells.

Embodiment 79. The method of embodiment 77 or 78, wherein said cancer cells are triple negative breast cancer cells.

SEQUENCE LISTING <110> City of Hope Fong, Yuman Chen, Nanhai <120> Chimeric Poxvirus Compositions and Uses Thereof <130> 48440-606001WO <150> US 62/372,408 <151> 2016-08-09 <150> US 62/519,010 <151> 2017-06-13 <160> 54 <170> PatentIn version 3.5 <210> 1 <211> 189415 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 1 gagaaagaga taaaactttt ttacgactcc atcagaaaga ggtttaatat ttttgtgaga 60 ccatcgaaga gagaaagaga aagagatagt tagtctagat atttttctta gtacaaaagt 120 caatgtttta aaatatatgg acaagaattt gtctgtataa aaacttgtgt gaaattttgt 180 accaaagaaa aaatgtgagc agtatcccct acatggattt tactagatca tttatatacc 240 aaaaaatatt atacgatcta cgttttatta tatgatttta acgtgtaaat tataaacatt 300 attttatgat atacaattgt ctggtaacct agatgggcat aggggatgtt gataagctcg 360 acgagtatat gttgttggac gttattgttt aagaaatagt tgatgcatca gaaagagaat 420 aaaaaatatt ttagtgagac catcgaagag agaaagagat aaaacttttt tacgactcca 480 tcagaaagag gtttaatatt tttgtgagac catcgaagag agaaagagaa taaaaatatt 540 ttatgactcc attgaagaga gaaagagaaa atgagaatga gaataaaaat attttagtga 600 caccatcaga aagaggttta atatttttgt gagaccatcg aagagagaaa gagaataaaa 660 atattttatg actccattga agagagaaag agaaaatgag aatgagaata aaaatatttt 720 agtgacacca tcagaaagag gtttaatatt ttttatgaga ccatcaaaga gagaaagaga 780 ataaaaatat ttttgtaaaa ctttttttat gagaccatca aagagagaaa gagaataaaa 840 atatttttgt aaaacttttt ttatgagacc atcaaagaga gaaagagaat aaaaatattt 900 ttgtaaaact ttttttatga gaccatcaaa gagagaaaga gaataaaaat atttttgtaa 960 aacttttttt atgagaccat caaagagaga aagagaataa aaatattttt gtaaaacttt 1020 ttttatgaga ccatcaaaga gagaaagaga ataaaaaaat atttttgtaa aacttttttt 1080 atgagaccat cagaaagagg tttaatattt ttgtgatacc ctgaaaggaa ataggaatag 1140 gaatagtgtc ataatcgtat cacactattg agacagaaaa agaagaagtc gcgagaggta 1200 actttttgtt ttgcaaaccg gaatatagtg tccggtacac ttttttaatt cgtggtgtgc 1260 ctgaatcgtt cgattaaccc tactcatcca atttcagatg aatagagtta tcgattcaga 1320 cacacgcttt gagttttgtt gaatcgatga gtgaagtatc atcggttgca ccttcagatg 1380 ccgatccgtc gacatacttg acctcaagtt cagatgattc cttgcacatg tctccgatac 1440 gaacgctaaa ctctagattc ttgacacatt ttgtatcgac gatcgttgaa ccgatgatat 1500 cttcgtaact cactttctta tgagagatgt tagacccgag tactggatgg gtcttgatgt 1560 cgctgtcttt ctcttcttcg ctacatctga tgtcgataga cacctcacag tctttccatc 1620 agcggattct gagatggatt taatctgagg acatttggtg aatccaaagt tcattctcag 1680 acctccaccg atgatggagt aataagtggt aggaggatct acatcctcga ctgattccac 1740 ctcgggatct ggatctgact cggactctgt aatttccgtt acggattggc aaatctttatc 1800 atcggtcggt gtttggtctt gctttgtgac tttgataata acatcgattc ccatatgatg 1860 tttgttttct tcttccgtac acgatgagga tgattgctga agactggcag gcacatgcat 1920 gccagtacga tatattgttt catgattgct attgattgag tactgttctt tatgattcta 1980 cttccttacc gtgcaataaa ttagaatata ttttctactt ttacgagaaa ttaattattg 2040 tatttatggg tgaaaaactt actataaaaa gcgggtgggt ttggaattag tgatcagttt 2100 atgtatatcg caactaccgg gcatatggct acattaccca catgataaga gattgtatca 2160 gtttcgtagt cttgagtatt ggtattacta tatagtatat agatgtcgac gctagagtta 2220 ctgtctccga atgcggcatg atagtatcat tctttgcttt cgttaactgt ttggaggaag 2280 aatctttgtt attgcattta atctcgaaat tcagagtgca cacctttctc ctgtaaagaa 2340 tcctgaagtt gctaccttat taagaacgga gaagtatcca tcacgaaaga cgggattaca 2400 gtctttatga ttcatagtaa tagttagttc cgacgttgag atggattcgc tgagaccggt 2460 agtggtcgtc cgagtacacg atgtgtcgtt gacgggatac agattaattt ccacatcgat 2520 atagttaaag gtatttctgg gtacgggttt gagatcgtcg tacatgggaa atgaaatgtg 2580 actgtctgaa tgtatggctt taagatagct gtgataccgt atacaggtcg gtgtcggaga 2640 ttcgaatctc tttaaggcga cttatgtcac gatgatggaa tctatcttat cgaatgatat 2700 atttttcata aatacacttt tatagtcctc gtttaaacag aatttactat gtagttccgc 2760 gaatgactcg tcccttaata ggcagtaggc tagtatcttt tttacgtagt aatcgtcgta 2820 gggagagaca tcttgtagaa caacgattta atcataggta gagatacttt cagtctgtgg 2880 tggatgatgt cattcacaac atccgccttg tatatgatgt ttctgttttc aaacaccaag 2940 tcgaataccg tctttagtcg gaaggttgat gtcgtatccg atgtatgagg caacattgtt 3000 gttacaattt tgaaaggcgg tattatagta ttcgtctttc tgaatgtcga acctatctag 3060 tagataccgt agtatattga gagtgtatcc ttgattatgt tttatgaata gataaagtag 3120 atgttgtcct tcttcctttt gttcgtgcca attgagtaac attatgagaa tatgacctgt 3180 tgcacaatcg ttccatgatg ggtgtacaat caagattatt acgtatcctc gtatcggctc 3240 ctcgagataa aagagcatac accacacgag gactatgttt ggtatactgt tgaaggtaag 3300 tgtgtaaccg cgttaatgtt tgctccataa tctattatcg cgtagatgaa tcgcttctcg 3360 gctcgcatct tagtgtgact taacttgtaa taattgcttt tgtagaacgt ggatatgtgt 3420 ttacagtagt aatgaagaga agtgagtcca tcctcgtcga cgcaattagg gtcggatcct 3480 ttgtacagaa cgtaatagtt taagctccca ttgaatttat atctaagata acacagcaat 3540 agatcggatg atttactaaa gtcatcaatg gtgtccgtta gtatatcaaa gatcttgtta 3600 tcgattgata gtgaatgaat cagatagtgg tgtagaggaa tatgtccttt ttcatccttg 3660 ctatcaaagt tacgcatgcc gtggtgtaac aatatcttta atacagatgg attaaatcgt 3720 gtattcatcg tatagcaatg taatggagag ttacctcgtt tattcagatc gcagtgttta 3780 ataactagct taaacagatg agacgatgta tccacatcaa agaacgtaaa atacatatga 3840 caaacattgt tgacagaaac gtgaccttca ttcttaccgt cgtccataaa tacgttaggt 3900 atgtaccaca tactgtcgcg aacgatgcgt acaatctcgt ccatctcata atgatttact 3960 ttttcataat taaagatgtg aaagaaaaac agaacaatat atttttttag taatgtttat 4020 gcgagacata taaaataaac tccgtgttta tgatcatttt taacagcaac acattcaata 4080 ttgtattgtt atttttatat tatttacaca attaacaata tattattagt ttatattact 4140 gaattaataa tataaaattc ccaatcttgt cataaacaca cactgagaaa cagcataaac 4200 acaaaatcca tcaaaaatgt cgatgaaata tctgatgttg ttgttcgctg ctatgataat 4260 cagatcattc gccgatagtg gtaacgctat cgaaacgaca tcgccagaaa ttacaaacgc 4320 tacaacagat attccagcta tcagattatg cggtccagag ggagatggat attgtttaca 4380 cggtgactgt atccacgcta gagatattga cggtatgtat tgtagatgct ctcatggtta 4440 tacaggcatt agatgtcagc atgtagtatt agtagactat caacgttcag aaaacccaaa 4500 cactacaacg tcatatatcc catctcccgg tattatgctt gtatagtag gcattattat 4560 tattacgtgt tgtctattat ctgtttatag gttcactcga cgaactaaac tacctataca 4620 agatatggtt gtgccataat ttttataaat ttttttatga gtatttttac aaaaaaaatg 4680 tataaagtgt atgtcttatg tatatttata aaaatgctaa gtatgcgatg tatctatgtt 4740 atttgtattt atctaaacaa tacctctacc tctagatatt atacaaaaat tttttatttc 4800 ggcatattaa agtaaaatct agttaccttg aaaatgaata cagtgggtgg ttccgtatca 4860 ccagtaagaa cataatagtc gaatacagta tccgattgag attttgcata caatactagt 4920 ctagaaagaa atttgtaatc atcttctgg acgggagtcc atatatctgt atcatcgtct 4980 agtttatcag tgtcccatgc tatattcctg ttatcatcat tagttaatga aaataactct 5040 cgtgcttcag aaaagtcaaa tattgtatcc atacatacat ctccaaaact atcgcttata 5100 cgtttatctt taacgatacc tatacctaga tggttattta ctaacagaca ttttccagat 5160 ctattgacta taactcctat agtttccaca tcaaccaagt aatgatcatc tattgttata 5220 taacaataac ataactcttt tccattttta tcagtatgta tatctatatc aacgtcgtcg 5280 ttgtagtgaa tagtagtcat tgatctatta tatgaaacgg atatgtctag aacggcaatt 5340 gttttacgtc cagttaacac tttctttgat ttaaagtcta gagtctttgc aaacataata 5400 tccttatccg actttatatt tcctgtaggg tggtataatt ttattttgcc tccacatatc 5460 ggtgtttcca aatatattac tagacaatat tccatatagt tattagttaa gggtacccaa 5520 ttagaacacg tacgcttatt atcatcattt ggatcgtatt tcataaaagt tattgtacta 5580 tcgatgtcaa cacattctac attttttaat cgtctatata gtatttttct gatattttct 5640 ataatatcag aattgtcttc catcggaagt tgtatactat cggaatcagt tacatgttta 5700 aataattctc tgatgtcatt ccttatacaa tcaaattcat tattaaacag tttaatagtc 5760 tgtagacctt tatcgtcgta aatatccatt gtctttattag ttacgcttat ttttatgtgt 5820 tttacgttgc tttattatat tttataagaa tgattgtttg acgaatcacg agaactatta 5880 agacacatta ttaggtatat attataaaaa agtttttgat tacgatgtta taagaggaaa 5940 gaggacacat taacatcata catcaattaa ctacattctt ataacatcgt aatcaaaaga 6000 attgcaattt tgatgtataa caactgtcaa tgggttatgg aattgtatat tacatattat 6060 acggtatgtt ggtaacgaca aataccgatc ggtaattgtc tgccggtgta atagaattat 6120 atatatctat ctattacacc ggctgagtat gcataataat aagttgtggt agtatgatct 6180 ccatatttat aatttaggac tttgtattca gtatttttgg aatcataaaa aataaaaaaa 6240 agtttacta atttaaaatt taaaaagtat ttacattttt ttcactgttt agtcgcggat 6300 atggaattcg atcctgccaa aatcaataca tcatctatag atcatgtaac aatattacaa 6360 tacatagatg aaccaaatga tataagacta acagtatgca ttatccgaaa tattaataac 6420 attacatatt atatcaatat cacaaaaata aatacacatt tggctaatca atttcgggct 6480 tggaaaaaac gtatcgccgg aagggactat atgactaact tatctagaga tacaggaata 6540 caacaatcaa aacttactga aactatacgt aactgtcaaa aaaatagaaa catatatggt 6600 ctatatatac actacaattt agttattaat gtggttattg attggataac cgatgtgatt 6660 gttcaatcaa tattaagagg gttggtaaat tggtacatag ctaataatac ctatactcca 6720 aatacaccca ataatacaac aaccatttct gagttggata tcatcaaaat actggataaa 6780 tacgaggacg tgtatagagt aagtaaagaa aaagaatgtg gaatttgcta tgaagttgtt 6840 tactcaaaac gatagatact ttggtttatt ggattcgtgt actcatatat tttgcataac 6900 atgcatcaat atatggcata aaacacgaag agaaaccggt gcgtcggata attgtcctat 6960 atgtcgtacc cgttttagaa acataacaat gagcaagttc tataagctag ttaactaata 7020 aataaaaagt ttaatttgtt gacgacgtat gtcgttattt ttctcgtatg aaagattaaa 7080 ttcaattcaa ttcgttgttt ctaatataat ctgccgtatt ggatggattc tcaagacaat 7140 tgcatttaga ttatattatc atgaataaaa atagtagcac gcactacttc agccaaatat 7200 tcttttttga aacgccatct atcgtagtga ggacacaagt gaacctataa ttatcaaatt 7260 tattagtatc agtcacatga aggactttct gtagagtgac gattctacca tctatggtac 7320 taacggtttc atcctccttg ataccctcac ccaaatgttc tataaattta gcatcctcgt 7380 ccgatctcat atcctttgcc aaccaataca tgtagctaaa attaggcata aatttcacac 7440 atccagtgca acgaaattct ccagaagatg ttacgatgtt taggttagga catttgattt 7500 cgtcggcatt aacatatggg tgaacacacc catacatgaa agcgatgaga aataggattc 7560 tcatcttgcc aaaatatcac tagaaaaaat ttatttatca attttaaagg tataaaaaat 7620 acttattgtt gctcgaatat tttgtatttg atggtatacg gaagattaga aatgtaggta 7680 ttatcatcaa ctgattctat ggttttatgt attctatcat gtttcactat tgcgtcggaa 7740 ataatatcat atgcttccac atatatttta ttttgtttta actcataata ctcacgtaat 7800 tctggattat tggcatatct atgaataatt ttagctccat gatcagtaaa tattaatgag 7860 aacatagtat taccacctac cattattttt ttcatttcgt tcaattcttg attgcaaaga 7920 tctatataat cattatagcg ttgacttatg gactctggaa tcttagacga tgtacagtca 7980 tctataatca tggcatattt aatacattgt tttatagcat agtagttatc tacgatgtta 8040 gatatttctc tcaatgaatc aatcacacaa tctaatgtag gtttatgaca taatagcatt 8100 ttcagcagtt caatgtttct agattcgttg atggcaatgg ctatacatgt atatccgtta 8160 tttgatctaa tgttgacatc tgaaccggat tctagcagta aagatactag agattgttta 8220 ttatatctaa cagccttgtg aagaagtgtt tctcctcgtt tgtcaatcat gttaatgtct 8280 ttaagataag gtaggcaaat gtttatagta ctaagaattg ggcaagcata agacatgtca 8340 caaagaccct ttttgtatgt ataagtgtaa aaattataac attcatagtt ggatttacat 8400 aggtgtccaa tcgggatctc tccatcatcg agataattga tggcatctcc cttccttttt 8460 tagtagatat ttcatcgtgt aagaatcaat attaatattt ctaaagtatt cgtgtatagc 8520 ctctttattt accacagttc catattccac tagagggata tcgccgaatg tcatatactc 8580 aattagtata tgttggagga catccgagtt cattgttttc aatatcaaaa agatggtttc 8640 cttatcattt ctccatagtg gtacaatact acacattatt ccgtgcggct ttccattttc 8700 caaaaacaat ttgaccaaat ctaaatctac atctttattg tatctataat cactatttag 8760 ataatcagcc ataattactc gagtgcaaca tgttagatcg tctatatatg aataagcagt 8820 gttatctatt cctttcatta acaatttaac gatgtctata tctatatgag atgacttaat 8880 ataatattga agagctgtac aatagttttt atctatagaa gacggcttga ttccgtgatt 8940 aattagacat ttaacaactt ccggacgcac atatgctctc gtatccgact ttgaatacag 9000 atgagagatg atatacagat gcaatacggt accgcaattt cgtagttgat aatcatcata 9060 cgcgtatcag tactcgtcct cataaagaac actgcagcca ttttctatga acaaatcaat 9120 aattttagga acaggatcat tgtcattaca taattttcta taactgaacg atggttttca 9180 catttaacac tcaagtcaaa tccatgttct accaaccct ttatcaagtc aacgtctaca 9240 tttttggatt tcatatagct gaatatatta aagtcattta tgttgctaaa tccagtggct 9300 tctagtagag ccatcgctat atcctttaac tttaacatgt ctactatttg tgtattcttc 9360 taatggggta gctgtctcca atttttgcgt aatggattag tgccactgtc tagtagtagt 9420 ttgacgacct cgacattatt acaatgctca ttaaaaaggt atgcgtgtaa agcattattc 9480 ttgaattggt tcctggtatc attaggatct ctgtctctca acatctgttt aagttcatcg 9540 agagccacct cctcattttc cagatagtca aacattttga ctgaatgagc tactgtgaac 9600 tctatacacc cacacaacta atgtcattaa atattatttt tttgaatgta tttataccat 9660 gtcaaaaact tgtacaatta ttaataaaaa taatttagtg tttaaatttt accagttcca 9720 gattttacac ctccgttaac cccacttttt acaccactgg acgatcctcc tccccacatt 9780 ccaccgccac cagatgtata agttttagat cctttattac taccatcatg tccatggata 9840 aagacactcc acatgccgcc actactaccc cctttagaag acatattaat aagacttaag 9900 gacaagttta acaataaaat taatcacgag taccctacta ccaacctaca ctattatatg 9960 attatagttt ctatttttac agtaccttaa ctaaagtctc tagtcacaag agcaatacta 10020 ccaacctaca ctattatatg attatagttt ctatttttat aggaacgcgt acgagaaaat 10080 caaatgtcta atttctaacg gtagtgttga taaacgatta tcgtcaatgg atacctcctc 10140 tatcatgtcg tctattttct tactttgttc tattaactta ttagcattat atattatttg 10200 attataaaac ttatattgct tattagccca atctgtaaat atcggattat taacatatcg 10260 tttctttgta ggtttattta acatgtacat cactgtaagc atgtccgtac catttattt 10320 aatttgacgc atatccgcaa tttctttttc gcagtcggtt ataaattcta tatatgatgg 10380 atacatgcta catgtgtact tataatcgac taatatgaag tacttgatac atattttcag 10440 taacgattta ttattaccac ctatgaataa gtacctgtga tcgtctaggt aatcaactgt 10500 tttcttaata cattcgatgg ttggtaattt actcagaata atttccaata tcttaatata 10560 taattctgct atttctggga tatatttatc tgccagtata acacaaatag taatacatgt 10620 aaacccatat tttgttatta tattaatgtc tgcgccatta tctattaacc attctactag 10680 gctgacacta tgcgacttaa tacaatgata aagtatacta catccatgtt tatctatttt 10740 gtttatatca tcaatatacg gcttacaaag ttttagtatc gataacacat ccaactcacg 10800 catagagaag gtagggaata atggcataat atttattagg ttatcatcat tgtcattatc 10860 tacaactaag tttccatttt ttaaaatata ctcgacaact ttaggatctc tattgccaaa 10920 tttttgaaaa tatttattta tatgcttaaa tctatataat gtagctcctt catcaatcat 10980 acatttaata acattgatgt atactgtatg ataagataca tattctaaca atagatcttg 11040 tatagaatct gtaatcttt taagaattgt ggatattagg atattattac gtaaactatt 11100 acacaattct aaaatataaa acgtatcacg gtcgaataat agttgatcaa ctatataatt 11160 atcgattttg tgatttttct tcctaaactg tttacgtaaa tagttagata gaatattcat 11220 tagttcatga ccactatagt tactatcgaa taacgcgtca aatatttccc gtttaatatc 11280 gcatttgtca agataataat agagtgtggt atgttcacga taagtataat aacgcatctc 11340 ttttttgtgt gaaattaaat agtttatcac gtccaaagat gtagcataac catcttgtga 11400 cctagtaata atataataat agagaactgt tttacccatt ctatcatcat aatcagtggt 11460 gtagtcgtaa tcgtaatcgt ctaattcatc atcccaatta taatattcac cagcacgtct 11520 aatctgttct attttgatct tgtatccata ctgtatgttg ctacatgtag gtattccttt 11580 atccaataat agtttaaaca catctacatt gggatttgat gttgtagcgt atttctctac 11640 aatattaata ccatttttga tactatttat ttctatacct ttcgaaatta gtaatttcaa 11700 taagtctata tcgatgttat cagaacatag atattcgaat atatcaaaat cattgatatt 11760 tttatagtcg actgacgaca ataacaaaat cacaacatcg tttttgatat tattattttt 11820 cttggtaacg tatgccttta atggagtttc accatcatac tcatataatg gatttgcacc 11880 actttctatc aatgattgg cactgctggc atcgatgtta aatgttttac aactatcata 11940 gagtatctta tcgttaacca tgattggttg ttgatgctat cgcatttttt ggtttctttc 12000 atttcagtta tgtatggatt tagcacgttt gggaagcatg agctcatatg atttcagtac 12060 tgtagtgtca gtactattag tttcgatcag atcaatgtct agatctatag aatcaaaaca 12120 cgataggtca gaagataatg aatatctgta cgcttctttt tgtactgtaa cttctggttt 12180 tgttagatgg ttgcatcgtg ctttaacatc aatggtacaa attttatcct cgctttgtgt 12240 atcatattcg tctctagtat aaaattctat attcagatta tcatgcgatg tgtatacgct 12300 aacggtatca ataaacggag cacaccattt agtcataaca gtaatccaaa attttttaaa 12360 gtatatctta acgaaagaag ttgtgtcatt gtctacggtg tatggtacta gatcctcata 12420 agtgtatata tctagagtaa tgtttaattt attaaatggt tgataatatg gatcctcatg 12480 acaatttccg aagatggaaa tgagatatag acatgcaata aatctaatcg aagacatggt 12540 tactccttaa aaaaatacga ataatcacct tggctattta gtaagtgtca tttaacacta 12600 tactcatatt aatccatgga ctcataatct ctatacggga ttaacggatg ttctatatac 12660 ggggatgagt agttttcttc tttaacttta tactttttac taatcatatt tagactgatg 12720 tatgggtaat agtgtttaaa gagttcgttc tcatcatcag aataaatcaa tatctctgtt 12780 tttttgttat acagatgtat tacagcctca tatattacgt aatagaacgt gtcatctacc 12840 ttattaactt tcaccgcata gttgtttgca aatacggtta atcctttgac ctcgtcgatt 12900 tccgaccaat ctgggcgtat aatgaatcta aactttaatt tcttgtaatc attcgaaata 12960 atttttagtt tgcatccgta gttatcccct ttatgtaact gtaaatttct caacgcgata 13020 tctccattaa taatgatgtc gaattcgtgc tgtataccca tactgaatgg atgaactaac 13080 gaatatcaac ggcgttaata gtaatttact ttttcatctt tacatattgg gtactagttt 13140 tactatcata agtttataaa ttccacaagc tactatggaa taagccaacc atcttagtat 13200 accacacatg tcttaaagtt tattaattaa ttacatgttg ttttatatat atcgctacga 13260 atttaaagag aaatcagttt aggaagaaaa aaattatcta tctacatcat cacgtctctg 13320 tattctacga tagagtgcta ctttaagatg agacatatcc gtgtcatcaa aaatatactc 13380 cattaaaatg attattccgg cagcgaactt gatattggat atatcacaac ctttgttaat 13440 atctacgaca atagacagca gtcccatggt tccataaaca gtgagtttat ctttctttga 13500 agcgatagtt tgtagagatc ttataaaacc gtcaaacgac atcgcattta tatctttagc 13560 taattcatat atgttaccat cgtaatatct aaccgcgtct atcttaaacg tttccatcgc 13620 tttaaagacg tttccgatag atggtctcat ttcatcagtc atactgagcc aacaaatata 13680 atcgtgtata acatctttga tagaatcaga ctctaaagaa aacgaatcgg ctttattata 13740 cgcattcatg ataaacttaa tgaaaaatgt ttttcgttgt ttaagttgga tgaatagtat 13800 gtcttaataa ttgttattat ttcattaatt aatatttagt aacgagtaca ctctataaaa 13860 acgagaatga cataactagt tatcaaagtg tctaggacgc gtaattttca tatggtatag 13920 atcctgtaag cattgtctgt attctggagc tattttcttt atcgcattag taagttcaga 13980 atatgttata aatttaaatc gaataacgaa catgacttta gtaaagtcgt ctatattaac 14040 tcttttattt tctagccatc gtaataccat gtttaagata gtatattctc tagttactac 14100 gatctcatcg ttgtctagaa tatcacatac tgaatctaca tccaatttta gaaattggtc 14160 tgtgttacat atctcttcta tattattgtt gatgtattgt cgtagaaaac tattacgtag 14220 accattttct ttataaaacg aatatatagt actccaatta tctttaccga tatatttgca 14280 cacataatcc attctctcaa tcactacatc tttaagattt tcgttgttaa gatatttggc 14340 taaactatat aattctatta gatcatcaac agaatcagta tatatttttc tagatccaaa 14400 gacgaactct ttggcgtcct ctataatatt cccagaaaag atattttcgt gttttagttt 14460 atcgagatct gatctgttca tatacgccat gattgtacgg tacgttatga taaccgcata 14520 aaataaaaat ccattttcat ttttaaccaa tactattcat aattgagatt gatgtaatac 14580 tttgttactt tgaacgtaaa gacagtacac ggatccgtat ctccaacaag cacgtagtaa 14640 tcaaatttgg tgttgttaaa cttcgcaata ttcatcaatt tagatagaaa cttatactca 14700 tcatctgttt taggaatcca tgtattatta ccactttcca acttatcatt atcccaggct 14760 atgtttcgtc catcatcgtt gcgcagagtg aataattctt ttgtattcgg tagttcaaat 14820 atatgatcca tgcatagatc ggcaaagcta ttgtagatgt gatttttcct aaatctaata 14880 taaaactcgt ttactagcaa acactttcct gatttatcga ccaagacaca tatggtttct 14940 aaatctatca agtggtgggg atccatagtt atgacgcagt aacatagatt attacattct 15000 tgactgtcgc taatatctaa atatttattg ttatcgtatt ggattctgca tatagatggc 15060 ttgtatgtca aagatataga acacataacc aatttatagt cgcgctttac attctcgaat 15120 ctaaagttaa gagattaga aaacattata tcctcggatg atgttatcac tgtttctgga 15180 gtaggatata ttaaagtctt tacagatttc gtccgattca aataaatcac taaataatat 15240 cccacattat catctgttag agtagtatca ttaaatctat tatattttat gaaagatata 15300 tcactgctca cctctatatt tcgtacattt ttaaactgtt tgtataatat ctctctgata 15360 caatcagata tatctattgt gtcggtagac gataccgtta catttgaatt aatggtgttc 15420 cattttacaa cttttaacaa gttgaccaat tcatttctaa tagtatcaaa ctctccatga 15480 ttaaatattt taatagtatc cattttatat cactacggac acaaagtagc tgacataaac 15540 cattgtataa tttttatgtt ttatgtttat tagcgtacac attttggaag ttccggcttc 15600 catgtatttc ctggagagca agtagatgat gaggaaccag atagtttata tccgtacttg 15660 cacttaaagt ctacattgtc gttgtatgag tatgatcttt taaacccgct agacaagtat 15720 ccgtttgata ttgtaggatg tggacattta acaatctgac acgtgggtgg atcggaccat 15780 tctcctcctg aacacaggac accagagtta ccaatcaacg aatatccact attgcaacta 15840 taagttacaa cgctcccatc ggtataaaaa tcctcgtatc cgttatgtct tccgttggat 15900 atagatggag gggattggca tttaacagat tcacaaatag gtgcctcggg attccatacc 15960 atagatccag tagatcctaa ttcacaatac gatttagatt caccgatcaa ctgatatccg 16020 ctattacaag agtacgttat actagagcca aagtctactc cgccaatatc aagttggcca 16080 ttatcgatat ctcgaggcga tgggcatctc cgtttaatac attgattaaa gagtgtccat 16140 ccagtacctg tacatttagc atatataggt cccatttttt gctttctgta tccaggtaga 16200 catagatatt ctatagtgtc tcctatgttg taattagcat tagtttccac actattctta 16260 aattttatat taatgggacg tgaaggaata ggacagtatg atagaacgca tcctattccc 16320 aacaatgtca ggaacgtcac gctctccacc ttcatattta tttatccgta aaaatgttat 16380 cctggacatc gtacaaataa taaaaaagcc catatatgtt tgctattgta gaaattgttt 16440 ttcacagttg ctcaaaaacg atggcagtga cttatgagtt tcatctttag taaacatatc 16500 ataatattcg atattacgag ttgacatatc gaacaaattc caagtatttg attttggata 16560 atattcgtat tttgcatctg ctataattaa gatataatca ccgcaagaac acacgaacat 16620 ctttcctaca tggttaaagt acatgtataa ttctatccat ttgtcttcct taactatata 16680 tttgtataga taattacgag tctcataagt aattccagta attgcataga tgtcaccatc 16740 gtactctaca gcataaacta tactatgatg tctaggcatg ggagactttt ttatccaacg 16800 atttttagtg aaacattcta catcgtttaa tactacatat ttctcatacg tggtataaac 16860 tccacccatt acatatatat catcgtttac gaataccgac gcgcctgaat atctaggagt 16920 aattaagttt ggaagtctta tccatttcga agtgccgtgt ttcaaatatt ctgccacacc 16980 cgttgaaata gaaaattcta atcctcctat tacatataac tttccatcgt taacacaagt 17040 actaacttct gattttaacg acgacatatt agtaaccgtt ttccattttt tcgttttaag 17100 atctacccgc gatacggaat aaacatgtct attgttaatc atgccgccaa taatgtatag 17160 acaattatgt aaaacatttg cattatagaa ttgtctatct gtattaccga ctatcgtcca 17220 atattctgtt ctaggagagt aatgggttat tgtggatata taatcagagt ttttaatgac 17280 tactatatta tgttttatac catttcgtgt cactggcttt gtagatttgg atatagttaa 17340 tcccaacaat gatatagcat tgcgcatagt attagtcata aacttgggat gtaaaatgtt 17400 gatgatatct acatcgtttg gatttttatg tatccacttt aataatatca tagctgtaac 17460 atcctcatga tttacgttaa cgtcttcgtg ggataagata gttgtcagtt catcctttga 17520 taattttcca aattctggat cggatgtcac cgcagtaata ttgttgatta tttctaacat 17580 cgacgcatta tatagttttt taattccata ttgtttagaa aagttaaaca tccttataca 17640 atttgtgggaa ttaatattat gaatcatagt ttttacacat agatctacta caggcgtaac 17700 atcaattatt acggcagcaa ctagtatcat ttctacattg tttatggtga tgtttatctt 17760 cttccagcgc atatagtcta atagcgattc aaacgcgtga tagtttatac cattcaatat 17820 aatcacttca tcatttatat ggtgctcctg aatgcgttta aaaaaattat acggagacgc 17880 cgtaataatt tccttattca cttgtataat ttccccattg atagaaaata tcacgctttc 17940 cattcttgaa gtactataag taattatagt ataatgtaaa cgtttatata ttcaatattt 18000 ttataaaaat cattttgaca ttaattcctt tttaaatttc cgtctatcat ctatagaaac 18060 gtattctatg aatttataaa atgcttttac gtgtcctatc gtaggcgata gaaccgctaa 18120 aaagcctatc gaatttctac aaaagaatct attatatggt atagggagag tataaaacat 18180 taaatgcccg tacttattaa agtattcagt agccaatcct aactctttcg aatacttatt 18240 aatggctctt gttctgtacg aatctatttt tttgaacaac ggacctagtg gtatatcttg 18300 ttctatgtat ctaaaataat gtctgactag atccgttagt ttaatatcct cagtcatctt 18360 gtctagaatg gcaaatctaa ctgcgggttt aggctttagt ttagttttta tatctacatc 18420 tatgtcttta tctaacacca aaaatataat agctaatatt ttattacaat catccggata 18480 ttcttctacg atctcactaa ctaatgtttc tttggttata ctagtatagt cacgatcaga 18540 caaataaaga aaatcagatg atcgatgaat aatacattta aattcatcat ctgtaagatt 18600 tttgagatgt ctcattaaaa tattattagg gttagtactc attatcattc ggcagctatt 18660 acttatttta ttattttca ccatatagat caatcattag atcatcaaaa tatgtttcaa 18720 tcatcctaaa gagtatggtg aatgactctt cccatctaat ttctgaacgt tcaccaatgt 18780 ctctagccac tttggcacta atagcgatca ttcgcttagc gtcttctata ttattaactg 18840 gttgattcaa tctatctagc aatggaccgt cggacagcgt cattctcatg ttcttaatca 18900 atgtacatac atcgccgtca tctaccaatt catccaacaa cataagcttt ttaaaatcat 18960 cattataata ggtttgatcg ttgtcatttc tccaaagaat atatctaata agtagagtcc 19020 tcatgattag ttaacaacta ttttttatgt taaatcaatt agtacaccgc tatgtttaat 19080 acttattcat attttagttt ttaggattga gaatcaatac aaaaaattaa tgcatcatta 19140 attttagaaa tacttagttt ccacgtagtc aatgaaacat ttgaactcat cgtacaggac 19200 gttctcgtac aggacgtaac tataaaccgg tttatatttg ttcaagatag atacaaatcc 19260 gataactttt tttacgaatt ctacgggatc cactttaaaa gtgtcatacc gggttctttt 19320 tattctttta aacagatcaa tggtgtgatg ttgattaggt cttttacgaa tttgatatag 19380 aatagcgttc acatatcctc cataatggtc aatcgccatt tgttcgtatg tcataaattc 19440 tttaattata tgacactgtg tattatttag ttcatccttg ttcatcatta ggaatctatc 19500 caaaatggca attatactag aactataggt gcgttgtata cacatattga tgtgtctgtt 19560 tatacaatcc atgatatttg gatccatgct actaccttcg ggtaaaattg tagcatcata 19620 taccatttct agtactttag gttcattatt atccattgca gaggacgtca tgatcgaatc 19680 ataaaaaaat atattatttt tatgttattt tgttaaaaat aatcatcgaa tacttcgtaa 19740 gatactcctt catgaacata atcagttaca aaacgtttat atgaagtaaa gtatctacga 19800 tttttacaaa agtccggatg cataagtaca aagtacgcga taaacggaat aataatagat 19860 ttatctagtc tatctttttc tatagctttc atagttagat acatggtctc agaagtagga 19920 ttatgtaaca tcagcttcga taaaatgact gggttattta gtcttacaca ttcgctcata 19980 catgtatgac cgttaactac agagtctaca ctaaaatgat tgaacaatag atagtctacc 20040 attgtttcgt attcagatag tacagcgtag tacatggcat cttcacaaat tatatcattg 20100 tctaatagat atttgacgca tcttatggat cccacttcaa cagccatctt aaaatcggta 20160 aaatcatatt gctttccttt atcattaata atttctaaaa catcatctct atcataaaag 20220 atacaaatat taactgtttg atccgtaata acattgctag tcgatagcaa tttgttaata 20280 agatgcgctg ggctcaatgt cttaataaga aggttaagag gactatctcc gaatttgttt 20340 tgtttattaa catccgttga tggaagtaaa agatctataa tgtctacatt cttgactgtt 20400 ttagagcata caatatggag aggtgtattt ccatcatgat ctggttttga gggactaatt 20460 cctagtttca tcatccatga gattgtagaa gcttttggat tgtctgacat aagatgtcta 20520 tgaatatgat ttttgccaaa tttatccact atcctggctt cgaatccgat ggacattatt 20580 tttttaaaca ctctttctga aggatctgta cacgccaaca acggaccaca tccttcttca 20640 tcaaccgagt tgttaatctt ggctccatac tgtaccaata aatttattct ctctatgact 20700 tcatcatctg ttcccgagag ataatataga ggtgttttat tatgtttatc acacgcgttt 20760 ggatctgcgc cgtgcgtcag cagcatcgcg actattctat tattattaat tttagaagct 20820 atatgcaatg gataatttcc atcatcatcc gtctcatttg gagagtatcc tctatgaaga 20880 agttcttcga caaatcgttc atctagtcct ttaattccac aatacgcatg tagaatgtga 20940 taattatttc cagaaggttc gatagcttgt agcatattcc taaatacatc taaattttta 21000 ctattatatt tggcataaag agatagataa tactcggccg acataatgtt gtccattgta 21060 gtataaaaat taatatttct atttctattt ctgtatattt gcaacaattt actctctata 21120 acaaatatca taacttagtt cttttatgtc aagaaggcac tggtttagtt catctataaa 21180 tgtcacgcca taactaccac gcatgccata ctcagaatta tgataaagat atttatcctt 21240 ggggtgtagg taatggggat taatctttgt tggatcagtc tctaagttaa cacatgtcac 21300 acatgatcca tttatagtta tatcacacga tgatgattta tgaattgatt ccggaagatc 21360 gctatcgtat tttgtggttc cacaattcat ttccatacat gttattgtca cactaatatt 21420 atgatgaact ttatctagcc gctgagtggt aaacaacaga acagatagtt tattatcttt 21480 accaacaccc tcagccgctg ccacaaatct ctgatccgta tccatgatgg tcatgtttat 21540 ttctagtccg tatccagtca acactatgtt agcatttctg tcgatatagc tttcactcat 21600 atgacactca ccaataatag tagaattaat gtcgtaattt acaccaatag tgagttcggc 21660 ggcaaagtac caataccggt aatcttgtcg aggaggacat atagtattct tgtattctac 21720 tgaatacccg agagatgcga tacaaaagag taagactaat ttgtaaacca tcttactcaa 21780 aatatgtaac aatagtacga tgcaatgagt aagacaatag gaaatctatc ttatatacac 21840 ataattattc tatcaatttt accaattagt tagtgtaatg ttaacaaaaa tgtggggagaa 21900 tctaattagt ttttctttac acaattgacg tacatgagtc tgagttcctt gtttttgcta 21960 attatttcat ccaatttatt attcttgact atatcgagat cttttgtata ggaggtcagac 22020 ttgtattcaa catgcttttc tataatcatt ttagctattt cggcatcatc caatagtaca 22080 ttttccagat tagcagaata gatattaatg tcgtatttga acagagcctg taacatctca 22140 atgtctttat tatctatagc caatttaatg tccggaatga agagaaggga attattggtg 22200 tttgtcgacg tcatatagtc gagcaagaga atcatcatat ccacgtgtcc attttttata 22260 gtggtgtgaa tacaactaag gagaatagcc agatcaaaag tagatggtat ctctgaaaga 22320 aagtaggaaa caatacttac atcattaagc atgacggcat gataaaatga agttttccat 22380 ccagttttcc catagaacat cagtctccaa tttttcttaa caaacagttt taccgtttgc 22440 atgttaccac tatcaaccgc ataatacaat gcggtgtttc ccttgtcatc aaattgtgaa 22500 tcatccagtc cactgaatag caaaatcttt actattttgg tatcttccaa tgtggctgcc 22560 tgatgtaatg gaaattcatt ctctagaaga tttttcaatg ctccagcgtt caacaacgta 22620 catactagac gcacgttatt atcagctatt gcataataca aggcactatg tccatggaca 22680 tccgccttaa atgcatcttt gctagagaga aagcttttca gctgcttaga cttccaagta 22740 ttaattcgtg acagatccat gtctgaaacg agacgctaat tagtgtatat tttttcattt 22800 tttataattt tgtcatattg caccagaatt aataatatct ctaatagatc tgattagtag 22860 atacatggct atcgcaaaac aacatataca catttaataa aaataatatt tattaagaaa 22920 attcagattt cacgtaccca tcaatataaa taaaataatg attccttaca ccgtacccat 22980 attaaggaga ttccacctta cccataaaca atataaatcc agtaatatca tgtctgatga 23040 tgaacacaaa tggtgtatta aattccagtt tttcaggaga tgatctcgcc gtagctacca 23100 tgatagtaga tgcctctgct acagttcctt gttcgtcgac atctatcttt gcattctgaa 23160 acattttata aatatataat gggtccctag tcatatgttt aaacaacgca ttatctggat 23220 taaacatact aggagccatc atttcggcta tcgacttaat atccctctta ttttcgatag 23280 aaaatttagg gagtttaaga ttgtacactt tattccctaa ttgaaacgac caatagtcta 23340 attttgcagc cgtaatagaa tctgtgaaat gggtcatatt atcacctatt gccaggtaca 23400 tactaatatt agcatcctta tacggaaggc gtaccatatc atattcttcg tcatcgattg 23460 tgattgtatt tccttgcaat ttagtaacta cgttcatcat gggaaccgtt ttcgtaccgt 23520 acttattagt aaaactagca ttgcgtgttt tagtgatatc aaacggatat tgccatatac 23580 ctttaaaata tatagtatta atgattgccc atagagtatt attgtcgagc atattagaat 23640 ctactacatt agacataccg gatctacgtt ctactataga attaatttta ttaaccgcat 23700 ctcgtctaaa gtttaatcta tataggccga atctatgata ttgttgataa tacgacggtt 23760 taatgcacac agtattatct acgaaacttt gataagttag atcagtgtac gtatatttag 23820 atgttttcag cttagctaat cctgatatta attctgtaaa tgctggaccc agatctcttt 23880 ttctcaaatc catagtcttc aataattcta ttctagtatt acctgatgca ggcaatagcg 23940 acataaacat agaaaacgaa taaccaaacg gtgagaagac aatattatca tcttgaatat 24000 ttttatacgc tactataccg gcattggtaa atccttgcag acgataggta gacactgaac 24060 acgttaacga tagtatcaat aacgcaatca tgattttatg gtattaataa ttaaccttat 24120 ttttatgttc ggtataaaaa ttatgatgt ctacacatcc ttttgtaatt gacatctata 24180 tatccttttg tataatcaac tctaatcact ttaactttta cagttttccc taccagttta 24240 tccctatatt caacatatct atccatatgc atcttaacac tctctgccaa gatagcttca 24300 aagtgaggat agtcaaaaag ataaatatat agagcataat cattctcgta tactctgccc 24360 tttattacat cacccgcatt gggcaacgaa taacaaaatg caagcatctt gttaacgggc 24420 tcgtaaattg ggataaaaat tatgttttta tatctatttt attcaagaga atattcagga 24480 atttcttttt ccggttgtat ctcatcgcag tatatatcat ttgtacattg tttcatattt 24540 tttaatagtc tacacctttt agtaggacta gtatcgtaca attcatagct gtattttgaa 24600 ttccaatcac gcataaaaat atcttccaat tgttgacgaa gacctaatcc atcatccggt 24660 gtaatattaa tagatgctcc acatgtatcc gtaaagtaat ttcctgtcca atttgaggta 24720 cctatatacg ccgttttatc ggttaccata tatttggcat ggtttaccct agaatacgga 24780 atgggaggat cagcatctgg tacaataaat agctttactt ctatattat gtttttagat 24840 tttagcatag cgatagatct taaaaagttt ctcatgataa acgaagatcg ttgccagcaa 24900 ctaatcaata gcttaacgga tacttgtctg tctatagcgg ctcttcttaa ttcatcttct 24960 atataaggcc aaaacaaaat attgcctgcc ttcgaataaa taatagggat aaagttcata 25020 acagatacat aaacgaattt actcgcattt ctaatacatg acaataaagc ggttaaatca 25080 ttggttcttt ccatagtaca tagttgttgc ggtgcagaag caataaatac agagtgtgga 25140 acaccactta cgttaatact aagaggatga tctgtattat aatacgacgg ataaaagttt 25200 ttccaattat atggtagatt gttaactcca agataccagt atacctcaaa aatttgagtg 25260 agatccgctg ccaagttcct attattgaag atcgcaatac ccaattcttt gacctgagtt 25320 agtgatctcc aatccatgtt agcgcttcct aaataaatat gtgtattatc agatatccaa 25380 aattttgtat gaagaactcc tcctaggata tttgtaatat ctatgtatcg tacttcaact 25440 ccggccattt gtagtctttc aacatccttt aatggtttgt tagatttatt gacggctact 25500 ctaactctta ctcctctttt gggtaattgt acaatctcgt ttaatattat cgtgccgaaa 25560 ttcgtaccca cttcatccga taaactccaa taaaaagatg atatatctag tgtttttgtg 25620 gtattggata gaatttccct ccacatgtta aatgtagaca aatatacttt atcaaattgc 25680 atacctatag gaatagtctc tgtaatcact gcgattgtat tatccggatt cattttattt 25740 gttaaaaaat aatcctatat cacttcactc tattaaaaat ccaagtttct atttctttca 25800 tgactgattt tttaacttca tccgtttcct tatgaagatg atgtttggca ccttcataaa 25860 ttttatttc tctattacaa tttgcatgtt gcatgaaata atatgcacct aaaacatcgc 25920 taatctcatt gtttgttccc tggagtatga gagtcggggg gtgttaatct tgggaattat 25980 ttttctaacc ttgttggtag ccttcaagac ctgactagca aatccagcct taattttttc 26040 atgattgatt aatgggtcgt attggtattt ataaacttta tccatatctc tagatactga 26100 ttctggacat agctttccga ctggcgcatt tggtgtgatg gttcccataa gtttggcagc 26160 tagcagattc agttttgaaa cagcatctgc attaactaga ggagacatta gaatcattgc 26220 tgtaaacaag tttggattat cgtaagaggc tagtatagaa attgttgctc ccatggaatg 26280 cccaataaga agactggaac tcctaaataa gtagatttaa tagttaccac gtgctgtacc 26340 acatctctaa catacgtacc aaagtcatca atcatcattt tttcaccatt acttcttcca 26400 tgtccaatat gatcatgtga gaatactaaa attcctaacg atgatatgtt ttcagctagt 26460 tcgtcataac gtccagaatg tttaccagct ccatgactta tgaatactaa tgccttagga 26520 tatgtaatag gtttccaata tatgtaatca ttgtccagat tgaacataca gtttgcactc 26580 atgattcacg ttatataact atcaatatta acagttcgtt tgatgatcat attattttta 26640 tgttttattg ataattgtaa aaacatacaa ttaaatcaat atagaggaag gagacggcta 26700 ctgtcttttg tgagatagtc atggcgacta aattagatta tgaggatgct gtttttact 26760 ttgtggatga tgataaaata tgtagtcgcg actccatcat cgatctaata gatgaatata 26820 ttacgtggag aaatcatgtt atagtgttta acaaagatat taccagttgt ggaagactgt 26880 acaaggaatt gatgaagttc gatgatgtcg ctatacggta ctatggtatt gataaaatta 26940 atgagattgt cgaagctatg agcgaaggag accactacat caattttaca aaagtccatg 27000 atcaggaaag tctattcgct accataggaa tatgtgctaa aatcactgaa cattggggat 27060 acaaaaagat ttcagaatct agattccaat cattgggaaa cattacagat ctgatgaccg 27120 acgataatat aaacatcttg atactttttc tagaaaaaaa attgaattga tgatataggg 27180 gtcttcataa cgcataatta ttacgttagc attctatatc cgtgttaaaa aaaattatcc 27240 tatcatgtat ttgagagttt tatatgtagc aaacatgata gctgtgatgc caataagctt 27300 tagatattca cgcgtgctag tgttagggat ggtattatct ggtggtgaaa tgtccgttat 27360 ataatctaca aaacaatcat cgcatatagt atgcgatagt agagtaaaca tttttatagt 27420 ttttactgga ttcatacatc gtctacccaa tttggttata aatgaaattg tcgccaatct 27480 tacacccaac cccttgttat ccattagtat agtattaact tcgttattta tgtcataaac 27540 tgtaaatgat tttgtagatg ccatatcata catgatattc atgtccctat tataatcatt 27600 actaacttta tcacaatata tgttgataat atctatatat gatctagtct ttgtgggcaa 27660 ctgtctatac aagtcgtcta aacgttgttt actcatatag tatcgaacag ccatcattac 27720 atggtcccgt tccgttgata gataatcgag tatgttagtg gacttgtcaa atctatatac 27780 catattttct ggaagtggat atacatagtc gtgatcaaca ttattgctag cctcatcttc 27840 tatatcatgt actataccat tatctatatc atctacataa tctacgatat tattacacat 27900 aaacatcgac aacatactat tgtttattat ctaagtcctg ttgatccaaa cccttgatct 27960 cctctatttg tactatctag agattgtact tcttccagtt ctggataata tatacgttga 28020 tagattagct gagctattct atctccagta tttacattaa acgtacattt tccattatta 28080 ataagaatga ctcctatgtt tcccctataa tcttcgtcta ttacaccacc tcctatatca 28140 atgcctttta gtgacagacc agacctagga gctattctac catagcaaat cttaggcatg 28200 gacatactaa tatctgtctt aattaactgt ctttctcctg gagggatagt ataatcgtaa 28260 gcgctataca aatcatatcc ggcagcaccc ggcgattgcc tagtaggaga tttagctctg 28320 ttagtttcct taacaaatct aactggtgag ttaatattca tgttgaacat aaaactaata 28380 ttattatttca aaattattta ccatcccata tattccatga ataagtgtga tgattgtaca 28440 cttctatagt atctatatac gattcacgat aaaatcctcc tatcaatagc agtttattat 28500 ccactatgat caattctgga ttatccctcg gataaatagg atcatctatc agagtccatg 28560 tattgctgga ttcacaataa aattccgcat ttctaccaac caagaataac cttctaccga 28620 acactaacgc gcatgattta taatgaggat aataagtgga tggtccaaac tgccactgat 28680 catgattggg tagcaaatat tctgtagttg tatcagtttc agaatgtcct cccattacgt 28740 atataacatt gtttatagat gccactgctg gattacatct aggtttcaga agactcggca 28800 tattaaccca agcagcatcc ccgtggaacc aacgctcaac agatgtggga tttggtagac 28860 ctcctactac gtataattta ttgttagcgg gtatcccgct agcatacagt ctggggctat 28920 tcatcggagg aattggaatc caattgtttg atatataatt tacagctata gcattgttat 28980 gtatttcatt gttcatccat ccaccgatga gatatactac ttctccaaca tgagtacttg 29040 tacacatatg gaatatatct ataatttgat ccatgttcat aggatactct atgaatggat 29100 acttgtatga tttgcgtggt tgtttatcac aatgaaatat tttggtacag tctagtatcc 29160 attttacatt atttatacct ctgggagaaa gataatttga cctgattca tttttgataa 29220 ggagtagcag atttcctaat ttatttcttc gctttatata ccacttaatg acaaaatcaa 29280 ctacataatc ctcatctgga acatttagtt catcgctttc tagaataagt ttcatagata 29340 gataatcaaa attgtctatg atgtcatctt ccagttccaa aaagtgtttg gcaataaagt 29400 ttttagtatg acataagaga ttggatagtc cgtattctat acccatcatg taacactcga 29460 cacaatattc ctttctaaaa tctcgtaaga taaagtttat acaagtgtag atgataaatt 29520 ctacagaggt taatatagaa gcacgtaata aattgacgac gttatgacta tctatatata 29580 cctttccagt atacgagtaa ataactatag aagttaaact gtgaatgtca aggtctagac 29640 aaaccctcgt aactggatct ttatttttcg tgtatttttg acgtaaatgt gtgcgaaagt 29700 aaggagataa ctttttcaat atcgtagaat tgactattat attgccacct atagcatcaa 29760 taattgtttt gaatttctta gtcatagaca atgctaatat attcttacag tacacagtat 29820 taacaaatat cggcatttat gtttctttaa aagtcaacat ctagagaaaa atgattatct 29880 ttttgagaca taactcccat tttttggtat tcacccacac gtttttcgaa aaaattagtt 29940 tttccttcca atgatatatt ttccatgaaa tcaaacggat tggtaacatt ataaattttt 30000 ttaaatccca attcagaaat caatctatcc gcgacgaatt ctatatatgt tttcatcatt 30060 tcacaattca ttcctataag tttaactgga agagccgcag taagaaattc ttgttcaatg 30120 gatactgcat ctgttataat agatctaacg gtttcttcac tcggtggata caataaatgt 30180 ttaaacatca aacatgcgaa gtcgcagtgt agaccctcgt ctctactaat tagttcgttg 30240 gaaaacgtga gtccgggcat taggccacgc tttttaagcc aaaatatgga agcgaatgat 30300 ccggaaaaga agattccttc tactgcagca aaggcaataa gtctctctcc ataaccggcg 30360 ctgtcatgta tccacttttg agcccaatcg gccttctttt ttacacaagg catcgtttct 30420 atggcattaa agagatagtt tttttcatta ctatctttaa cataagtatc gatcaaaaga 30480 ctatacattt ccgaatgaat gttttcaatg gccatctgaa atccgtagaa acatctagcc 30540 tcggtaatct gtacttctgt acaaaatcgt tccgccaaat tttcattcac tattccgtca 30600 ctggctgcaa aaaacgccaa tacatgtttt ataaaatatt tttcgtctgg tgttagttta 30660 ttccaatcat tgatatcttt agatatatct acttcttcca ctgtccaaaa tgatgcctct 30720 gcctttttat acatgttcca gatgtcataa tattggattg ggaaaataac aaatctattt 30780 ggatttggtg caaggatggg ttccataact aaattaacaa tatcaataaa ttttttttca 30840 gttatctata tgcctgtact tggatttttt gtacatcgat atcgccgcaa tcactacaat 30900 aattacaagt attattgata gcattgttat tagtactatc ataattaaat tatcgacatt 30960 catggggtgct gaataatcgt tattatcatc attatcattt tgtaattgtg acatcatact 31020 aaataaatcg tttgcgagat tgttgtggga agcgggcatg gaggatgcat tatcattatt 31080 atttaacgcc ttccatttgg attcacaaat gttacgcaca ttcaacattt tatggaaact 31140 ataattttgt gaaaacagat aacaagaaaa ctcgttatcg ttcaaatttt taacgatagt 31200 aaaccgatta aacgtcgagc taatttctaa cgctagcgac tctgttggat atgggtttcc 31260 agatatatat cttttcagtt cccctacgta tctataatca tctgtaggaa atggaagata 31320 tttccattta tctactgttc ctaatatcat atgtggtggt gtagtagaac cattaagcgc 31380 gaaagatgtt atttcgcatc gtattttaac ttcgcaataa tttctggtta gataacgcac 31440 tctaccagtc aagtcaatga tattagcctt tacagatata ttcatagtag tcgtaacgat 31500 gactccatct tttagatgcg atactccttt gtatgtacca gaatcttcgt acctcaaact 31560 cgatatattt aaacaagtta atgagatatt aacgcgtttt atgaatgatg atatataacc 31620 agaagtttta tcctcggtgg ctagcgctat aaccttatca ttataatacc aactagtgtg 31680 attaatatgt gacacgttag tgtgggtaca aatatgtaca ttatcgtcta cgtcgtattc 31740 gatacatccg catacagcca acaaatataa aatgacaaat actctaacgc cgttcgtacc 31800 catcttgatg cggtttaata aatgttttga tttcaattta ttgtaaaaaa agattcggtt 31860 ttatactgtt cgatattctc attgcttata ttttcatcta tcatctccac acagtcaaat 31920 ccgtggttag catgcacctc atcaaccggt aaaagactat cggactcttc tatcattata 31980 actctagaat atttaatttg gtcattatta atcaagtcaa ttatcttatt tttaacaaac 32040 gtgagtattt tactcatttt ttataaaaac ttttagaaat atacagactc tatcgtgtgt 32100 ctatatcttc tttttatatc caatgtattt atgtctgatt tttcttcatt tatcatatat 32160 aatggtccaa attctacacg tgcttcggat tcatccagat cattaaggtt cttataattg 32220 taacatcctt ctcttccctc ttctacatct tccttcttat tcttattctt agcgtcacag 32280 aatctaccac agcaggatcc catgacgagc gtcatattaa actaattcat tttcaattat 32340 aatatactgg taatgaccat taaaataaaa atattcttca taaccggtaa gaaagtgaaa 32400 agttcacatt gaaactatgt cagtagtata catcatgaaa tgagatgaaa tgatgatata 32460 tatactctat tttggtggag gattatatga tataattcgt ggataatcat ttttaagaca 32520 catttcttta ttcgtaaatc ttttcacgtt aaatgagtgt ccatattttg caatttcttc 32580 atatgatggc ggtgtacgtg gacgaggctg ctcctgttct tgttgtagtc gccgactgtc 32640 gtgtttgcgt ttagatccct ccattatcgc gattgcgtag atggagtact attatatacc 32700 ttgtaattaa atttttttat taattaaacg tataaaaacg ttccgtatct gtatttaaga 32760 gccagatttc gtctaataga acaaatagct acagtaaaaa taactagaat aattgctaca 32820 cccactagaa accacggatc gtaatacggc aatcggtttt cgataatagg tggaacgtat 32880 attttattta aggacttaac aattgtctgt aaaccacaat ttgcttccgc ggatcctgta 32940 ttaactatct gtaaaagcat atgttgaccg ggcggagccg aacattctcc gatatctaat 33000 ttctgtatat ctataatatt attaacctcc gcatacgcat tacagttctt ttctagcttg 33060 gataccgcac taggtacatc gtctagatct attcctattt cttcagcgat agctcttcta 33120 tccttttccg gaagcaatga aatcacttca ataaatgatt caaccatgag tgtgaaacta 33180 agtcgagaat tactcatgca tttgttagtt attcggagcg cgcaattttt aaactgtcct 33240 ataacctctc ctatatgaat agcacaagtg acattagtag ggatagaatg ttgagctaat 33300 ttttgtaaat aactatctat aaaaagatta tacaaagttt taaactcttt agtttccgcc 33360 atttatccag tctgagaaaa tgtctctcat aataaatttt tccaagaaac taattgggtg 33420 aagaatgggaa acctttaatc tatatttatc acagtctgtc ttggtacaca tgatgaattc 33480 ttctaatgct gtactaaatt cgatatcttt ttcgatttct ggatatgttt ttaataaagt 33540 atgaacaaag aaatggaaat cgtaatacca gttatgttta actttgaaat tgttttttat 33600 tttcttgtta atgattccag ccacttggga aaagtcaaag tcgtttaatg ccgatttaat 33660 acgttcatta aaaacaaact ttttatcctt tagatgaatt attattggtt cattggaatc 33720 aaaaagtaag atattatcgg gtttaagatc tgcgtgtaaa aagttgtcgc agcatggtag 33780 ttcgtaaatt ttaatgtata acagagccat ctgtaaaaag ataaacttta tgtattgtac 33840 caaagattta aatcctaatt tgatagctaa ctcggtatct actttatctg cagaatacag 33900 tgctagggga aaaattataa tatttcctct ttcgtattcg tagttagttc tcttttcatg 33960 ttcgaaaaag tgaaacatgc ggttaaaata gtttataaca ttaatattac tgttaataac 34020 tgccgggtaa aagtgggata gtaatttcac gaatttgata ctgtcctttc tctcgttaaa 34080 cgcctttaaa aaaactttag aagaatatct caatgagagt tcctgaccat ccatagtttg 34140 tatcaataat agcaacatat gaagaacccg tttatacaga gtatgtaaaa atgttaattt 34200 atagtttaat cccatggccc acgcacacac gattaatttt ttttcatctc cctttagatt 34260 gttgtataga aatttgggta ctgtgaactc cgccgtagtt tccatgggac tatataattt 34320 tgtggcctcg aatacaaatt ttactacata gttatctatc ttaaagacta taccatatcc 34380 tcctgtagat atgtgataaa aatcgtcgtt tataggataa aatcgtttat ccttttgttg 34440 gaaaaaggat gaattaatgt aatcattctc ttctatcttt agtagtgttt ccctattaaa 34500 attcttaaaa taatttaaca atctaactga cggagcccaa ttttggtgta aatctaattg 34560 ggacattata ttgttaaaat acaaacagtc tcctaatata acagtatctg ataatctatg 34620 gggagacatc cattgatatt caggggatga atcattggca acacccattt attgtacaaa 34680 aagccccaat ttacaaacga aagtccaggt ttgatagaga caaactatta actattttgt 34740 ctctgttttt aatttcttta gtaatgaaat tattcacaat atcagtatct tctttatcta 34800 ccagagattt tactaacttg ataaccttgg ctgtctcatt caatagggta gtaatatttg 34860 tatgtgtgat attgatatct ttttgaattg tttcttttag aagtgattct ttgatggtgc 34920 cagcatacga attacaataa tgcagaaact cggttaacat gcaggaatta tagtaagcca 34980 attccaattg ttgcctgtat tgtattagag tattaatatg cgcaatggtg tccttgcgtt 35040 tctctgatag aatgcgagca gcgattttgg cgttatcatt tgacgatatt tctggaatga 35100 cgaatcctgt ttctactaac tttttggtag gacaaagtga aacaatcaag aagatagctt 35160 ctcctcctat ttgtggaaga aattgaactc ctctagatga tctactgacg atagtatctc 35220 cttgacagat attggaccga attacagaag tacctggaat gtaaagccct gaaaccccct 35280 cattttttaa gcagattgtt gccgtaaatc ctgcactgtg accaagatag agagctcctt 35340 tggtgaatcc atctctatgt ttcagtttaa ccaagaaaca gtcagctggt ctaaaatttc 35400 catctctatc taatacagca tctaacttga tgtcaggaac tatgaccggt ttaatgttat 35460 atgtaacatt gagtaaatcc ttaagttcat aatcatcact gtcatcagtt atgtacgatc 35520 caaacaatgt ttctaccggc atagtggata cgaagatgct atccatcaga atgtttccct 35580 gattagtatt ttctatatag ctattcttct ttaaacgatt ttccaaatca gtaactatgt 35640 tcattttttt aggagtagga cgcctagcca gtatggaaga ggattttcta gatcctctct 35700 tcaacatctt tgatctcaat ggaatgcaaa accccatagt gaaacaacca acgataaaaa 35760 taatattgtt tttcactttt tataatttta ccatctgact catggattca ttaatatctt 35820 tataagagct actaacgtat aattctttat aactgaactg agatatatac accggatcta 35880 tggtttccat aattgagtaa atgaatgctc ggcaataact aatggcaaat gtatagaaca 35940 acgaaattat actagagttg ttaaagttaa tattttctat gagctgttcc aataaattat 36000 ttgttgtgac tgcgttcaag tcataaatca tcttgatact atccagtaaa cagtctttaa 36060 gttctggaat attatcatcc cattgtaaag cccctaattc gactatcgaa tatcctgctc 36120 tgatagcagt ttcaatatcg acggacgtca atactgtaat aaaggtggta gtattgtcat 36180 catcgtgata aactactgga atatggtcgt tagtaggtac ggtaacttta cacaacgcga 36240 tatataactt tccttttgta ccatttttaa cgtagttggg acgtcctgca gggtattgtt 36300 ttgaagaaat gatatcgaga acagatttga tacgatattt gttggattcc tgattattta 36360 ctataatata atctagacag atagatgatt cgataaatag aaaaggtata tcgttggtag 36420 gataatacat ccccattcca gtattctcgg atactctatt aatgacacta gttaagaaca 36480 tgtcttctat tctagaaaac gaaaacatcc tacatggact cattaaaact tctaacgctc 36540 ctgattgtgt ctcgaatgcc tcgtacaagg atttcaagga tgccatagat tctttgacca 36600 acgatttaga attgcgttta gcatctgatt tttttattaa atcgaatggt cggctctctg 36660 gtttgctacc ccaatgataa caatagtctt gtaaagataa accgcaagaa aatttatacg 36720 catccatcca aataacccta gcaccatcgg atgatattaa tgtattatta tagattttcc 36780 atccacagtt attgggccag tatactgtta gcaacggtat atcgaataga ttactcatgt 36840 aacctactag aatgatagtt cgtgtactag tcataatatc tttaatccaa tctaagaaat 36900 ataaaattag atcttttaca ctgttaaagt taacaaaggt attacccgga tacgtggata 36960 tcatatatgg cattggtcca ttatcagtaa tagctccata aactgatacg gcgatggttt 37020 ttatatgtgt ttgatctaac gaggaagaaa ttcgcgccca caattcatct ctagatatgt 37080 atttaatatc aaacggtaac acatcaattt cgggacgcgt atatgtttct aaatttttaa 37140 tccaaatata atgatgacct atatgcccta ttatcatact gtcaactata gtacacctag 37200 agaacttacg atacatctgt ttcctgtaat cgttaaattt tacaaatcta taacatgcta 37260 aaccttttga cgacaaccat tcattaattt ctgatatgga atctgtattc tcgataccgt 37320 attgttctaa agccagtgct atatctccct gttcgtggga acgctttcgt ataatatcga 37380 tcaacggata atctgaagtt tttggagaat aatatgactc atgatctatt tcgtccataa 37440 acaatctaga cataggaatt ggaggcgatg atcttaattt tgtgcaatga gtcgtcaatc 37500 ctataacttc taatcttgta atattcatca tcgacataat actatctatg ttatcatcgt 37560 atattagtat accatgacct tcttcatttc gtgccaaaat gatatacagt cttaaatagt 37620 tacgcaatat ctcaatagtt tcataattgt tagctgtttt catcaagatt tgtaccctgt 37680 ttaacatgat ggcgttctat acgtttctat tttctatttt ttaaattttt aacgatttac 37740 tgtggctaga tacccaatct ctctcaaata tttttttagc ctcgcttaca agctgtttat 37800 ctatactatt aaaactgacg aatccgtgat tttggtaatg ggttccgtcg aaatttgccg 37860 aagtgatatg aacatattcg tcgtcgacta tcaacaattt tgtattattc tgaatagtga 37920 aaaccttcac agatagatca ttttgaacac acaacgcgtc tagacttctg gcggttgcca 37980 tagaatatac gtcgttctta tcccaattac caactagaag tctgatctta actcctctat 38040 taatggctgc ttctataatg gagttgtaaa tgtcgggcca atagtagcta ttaccgtcga 38100 cacgtgtagt gggaactatg gccaaatgtt caatatctat actagtctta gctgacctga 38160 gtttatcaat aactacatcg gtatctagat ctctagaata tcccaatagg tgttccggag 38220 aatcagtaaa gaacactcca cctataggat tcttaatatg atacgcagtg ctaactggca 38280 gacaacaagc cgcagagcat aaattcaacc atgaattttt tgcgctatta aaggctttaa 38340 aagtatcaaa tcttctacga agatctgtgg ccagcggggg ataatcagaa tatacaccta 38400 acgttttaat cgtatgtata gatcctccag taaatgacgc gtttcctaca taacatcttt 38460 catcatctga cacccaaaaa caaccgagta gtagtcccac attatttttt ttatctatat 38520 taacggttat aaaatttata tccgggcagt gactttgtag ctctcccaga tttcttttcc 38580 ctcgttcatc tagcaaaact attattttaa tccctttttc agatgcctct tttagtttat 38640 caaaaataag cgctccccta gtcgtactca gaggattaca acaaaaagat gctatgtata 38700 tatatttctt agctagagtg ataatttcgt taaaacattc aaatgttgtt aaatgatcgg 38760 atctaaaatc catattttct ggtagtgttt ctaccagcct acattttgct cccgcaggta 38820 ccgatgcaaa tggccacatt tagttaacat aaaaacttat acatcctgtt ctatcaacga 38880 ttctagaata tcatcggcta tatcgctaaa attttcatca aagtcgacat cacaacctaa 38940 ctcagtcaat atattaagaa gttccatgat gtcatcttcg tttatttcta tatccgtatc 39000 cattgtagat tgttgaccga ttatcgagtt taaatcatta ctaatactca atccttcaga 39060 atacaatctg tgtttcattg taaatttata ggcggtgtat ttaagttggt agattttcaa 39120 ttatgtatca atatagcaac agtagttctt gctcctcctt gattctagca tcctcttcat 39180 tattttcttc tacgtacata aacatgtcca atacgttaga caacacaccg acgatggcgg 39240 ccgccacaga cacgaatatg actaaaccga tgaccattta aaaacccctc tctagctttc 39300 acttaaactg tatcgattat tcttttagaa catgtataat ataaaaacat tattctattt 39360 cgaatttagg cttccaaaaa tttttcatcc gtaaaccgat aataatatat atagacttgt 39420 taatagtcgg aataaataga ttaatgctta aactatcatc atctccacga ttagagatac 39480 aatatttaca ttctttttgc tgtttcgaaa ctttatcaat acacgttaat acaaacccag 39540 gaaggagata ttgaaactga ggctgttgaa aatgaaacgg tgaatacaat aattcagata 39600 atgtaaaatc atgattccgt attctgatga tattagaact gctaatggat gtcgatggta 39660 tgtatctagg agtatctatt ttaacaaagc atcgatttgc taatatacaa ttatcctttt 39720 gattaattgt tattttattc atattcttaa aaggtttcat atttatcaat tcttctacat 39780 taaaaatttc catttttaat ttatgtagcc ccgcaatact cctcattacg tttcattttt 39840 tgtctataat atccattttg ttcatctcgg tacatagatt atccaattga gaagcgcatt 39900 tagtagtttt gtacatttta agtttattga caaatcgtcg aaaactagtt atagttaaca 39960 tttattatt tgataccctg atattaatac ccctgccgtt actattattt ataactgatg 40020 taatccacgt aacattagaa ttaattatcg atagtaatgc atcgacgctt ccaaaattgt 40080 ctattataaa ctcaccgata atttttttat tgcatgtttt catattcatt aggattatca 40140 aatctttaat cttattacga ttgtatgcgt tgatattgca agacgtcatt ctaaaagacg 40200 gaggatctcc atcaaatgcc aaacaatcac gtacaaagta catggaaata ggttttgttc 40260 tattgcgcat catagattta tatagaacac ccgtagaaat actaatttgt tttactctat 40320 aaaatactaa tgcatctatt tcatcgtttt gtataacgtc tttccaagtg tcaaattcca 40380 aatttttttc attgatagta ccaaattctt ctatctcttt aactacttgc atagataggt 40440 aattacagtg atgcctacat gccgtttttt gaaactgaat agatgcgtct agaagcgatg 40500 ctacgctagt cacaatcacc actttcatat ttagaatata tgtatgtaaa aatatagtag 40560 aatttcattt tgtttttttc tatgctataa atgaattctc attttgcatc tgctcatact 40620 ccgttttata tcaataccaa agaaggaaga tatttggttc taaaagccgt taaagtatgc 40680 gatgttagaa ctgtagaatg tgaaggaagt aaagcttcct gcgtactcaa agtagataaa 40740 ccctcatcac ccgcgtgtga gagaagacct tcgtcccctt ccagatgcga gagaatgaat 40800 aacccaggaa aacaagttcc gtttatgagg acggacatgc tacaaaatat gttcgcggct 40860 aatcgcgata atgtagcttc tagacttttg tcctaaaata ctattatatc cttttcgata 40920 ttaataaatc cgtgtcgtcc aggtttttta tctctttcag tatgtgaata gataggtatt 40980 ttatctctat tcatcatcga atttaagaga tccgataaac attgtttgta ttctccagat 41040 gtcagcatct gatacaacaa tatatgtgca cataaacctc tggcacttat ttcatgtacc 41100 ttccccttat cactaaggag aatagtattt gagaaatatg tatacatgat attatcatga 41160 attagatata cagaatttgt aacactctcg aaatcacacg atgtgtcggc gttaagatct 41220 aatatatcac tcgataacac attttcatct agatacacta gacatttttt aaagctaaaa 41280 tagtctttag tagtgacagt aactatgcga ttatttcat cgatgataca tttcatcggc 41340 atattattac gcttaccatc aaagactata ccatgtgtat atctaacgta ttctagcatg 41400 gttgccatac gcgcattaaa cttttcagga tctttggata gatcttccaa tctatctatt 41460 tgagaaaaca tttttatcat gttcaatagt tgaaacgtcg gatccactat atagatatta 41520 tctataaaga ttttaggaac tacgttcatg gtatcctggc gaatattaaa actatcaatg 41580 atatgattat cgttttcatc ttttatcacc atatagtttc taagatatgg gattttactt 41640 aatataatat tatttcccgt gataaatttt attagaaagg ccaaatctat aagaaaagtc 41700 ctagaattag tctgaagaat atctatatcg ccgtatagta tatttggatt aattagatat 41760 agagaatatg atccgtaaca tatacaactt ttattatggc gtctaagata ttcttccatc 41820 aacttattaa catttttgac tagggaagat acattatgac gtcccattac ttttgccttg 41880 tctattactg cgacgttcat agaatttagc atatctcttg ccaattcttc cattgatgtt 41940 acattataag aaattttaga tgaaattaca tttggagctt taatagtaag aactcctaat 42000 atgtccgtgt atgtggtcac taatacagat tgtagttcta taatcgtaaa taatttacct 42060 atattatatg tttgagtctg tttagaaaag tagctaagta tacgatcttt tatttctgat 42120 gcagatgtat taacatcgga aaaaaatctt ttttattct tttttactaa agatacaaat 42180 atgtctttgt taaaaacagt tattttttga atatttctag cttgtaattt taacatatga 42240 tattcgttca cactaggtac tctgcctaaa taggtttcta taatctttaa tgtaatatta 42300 ggaaaagtat tctgatcagg attcctattc attttgagga tttaaaactc tgattattgt 42360 ctaatatggt ctctacgcaa actttttcac agagcgatag agtttttgat aactcgtttt 42420 tcttaagaaa tataaaacta ctgtctccag agctcgctct atcttttaatt ttatctaatt 42480 cgatacaaac tcctgatact ggttcagaaa gtaattcatt aattttcagt cctttataga 42540 agatatttaa tatagataat acaaaatctt cagtttttga tatcgatctg attgatccta 42600 gaactagata tattaataac gtgctcatta ggcagtttat ggcagcttga taattagata 42660 tagtatattc cagttcatat ttattagata ccgcattgcc cagattttga tattctatga 42720 attcctctga aaataaatcc aaaataacta gacattctat tttttgtgga ttagtgtact 42780 ctcttccctc tatcatgttc actactggtg tccacgatga taaatatcta gagggaatat 42840 aatatagtcc ataggatgcc aatctagcaa tgtcgaataa ctgtaatttt attcttcgct 42900 cttcattatg aattgattct tgaggtataa acctaacaca aattatatta ttagactttt 42960 cgtatgtaat gtctttcatg ttataagttt ttaatcctgg aatagaatct attttaatga 43020 ggcttttaaa cgcagagttc tccaacgagt caaagcataa tactctgttg tttttcttat 43080 atacgatgtt acgattttct tctttgaatg gaataggttt ttgaattagt ttataattac 43140 aacataatag ataaggaagt gtgcaaatag tacgcggaaa aaacataata gctcccctgt 43200 tttcatccat ggttttaagt aaatgatcac tggcttcttt agtcaatgga tattcgaaca 43260 ttaaccgttt catcatcatt ggacagaatc catatttttt aatgtaaaga gtgatcaaat 43320 cattgtgttt attgtaccat cttgttgtaa atgtgtattc ggttatcgga tctgctcctt 43380 tttctattaa agtatcgatg tcgatctcgt ctaagaattc aactatatcg acatatttca 43440 tttgtataca cataaccatt actaacgtag aatgtatagg aagagatgta acgggaacag 43500 ggtttgttga ttcgcaaact attctaatac ataattcttc tgttaatacg tcttgcacgt 43560 aatctattat agatgccaag atatctatat aattattttg taagatgatg ttaactatgt 43620 gatctatata agtagtgtaa taattcatgt attttgatat atgttccaac tctgtctttg 43680 tgatgtctag tttcgtaata tctatagcat cctcaaaaaa tatattcgca tatattccca 43740 agtcttcagt tctatcttct aaaaaatctt caacgtatgg aatataataa tctattttac 43800 ctcttctgat atcattaatg atatagtttt tgacactatc ttctgtcaat tgattcttat 43860 tcactatatc taagaaacgg atagcgtccc taggacgaac tactgccatt aatatctcta 43920 ttatagcttc tggacataat tcatctatta taccagaatt aatgggaact attccgtatc 43980 tatctaacat agttttaaga aagtcagaat ctaagacttg atgttcatat attggttcat 44040 acatgaaatg atctctattg atgatagtga ctatttcatt ctctgaaaat tggtaactca 44100 ttctatatat gctttccttg ttgatgaagg atagaatata ctcaatagaa tttgtaccaa 44160 caaactgttc tcttatgaat cgtatatcat catctgaaat aatcatgtaa ggcatacatt 44220 taacaattag agacttgtct cctgttatca atatactatt cttgtgataa tttatgtgtg 44280 aggcaaattt gtccacgttc tttaattttg ttatagtaga tatcaaatcc aatggagcta 44340 cagttcttgg cttaaacaga tatagttttt ctggaacgaa ttctacaaca ttattataaa 44400 ggactttggg tagataagtg ggatgaaatc ctattttaat taatgcgata gccttgtcct 44460 cgtgcagata tccaaacgct tttgtgatag tatggcattc attgtctaga aacgctctac 44520 gaatatctgt gacagatatc atctttagag aatatactag tcgcgttaat agtactacaa 44580 tttgtatttt ttaatctatc tcaataaaaa aattaatatg tatgattcaa tgtataacta 44640 aactactaac tgttattgat aactagaatc agaatctaat gatgacgtaa ccaagaagtt 44700 tatctactgc caatttagct gcattatttt tagcatctcg tttagatttt ccatctgcct 44760 tatcgaatac tcttccgtcg atatctacac aggcataaaa tgtaggagag ttactaggcc 44820 ccactgattc aatacgaaaa gaccaatctc tcttagttat ttggcagtac tcattaataa 44880 tggtgacagg gttagcatct ttccaatcaa taattttttt agccggaata acatcatcaa 44940 aagacttatg atcctctctc attgattttt cgcgggatac atcatctatt atggcgtcag 45000 ccataacatc agcatccggc ttatccgcct ccgttgtcat aaaccaacga ggaggaatat 45060 cgtcggagct gtacaccata gcactacgtt gaagatcgta cagagcttta ttaacttctc 45120 gcttctccat attaagttgt ctagttagtt gtgcagcagt agctccttcg attccaatgt 45180 ttttaatagc cgcacacaca atctctgcgt cagaacgctc gtcaatatag atcttagaca 45240 tttttagaga gaactaacac aaccagcaat aaaactaatt tattttatca ttttttattatt 45300 catcatcctc tggtggttcg tcgtttctat cgaatgtgga tctgattaac ccgtcatcta 45360 taggtgatgc tggttctgga gattctggag gagatggatt attatctgga agaatctctg 45420 ttatttcctt gttttcatgt atcgattgcg ttgtaacatt aagattgcga aatgctctaa 45480 atttgggagg cttaaagtgt tgtttgcaat ctctacacgc atgtctaact agtggaggtt 45540 cgtcagcggc tctagtttga atcatcatcg gcgtagtatt cctactttta cagttaggac 45600 acggtgtatt gtatttctcg tcgagaacgt taaaataatc gttgtaactc acatccttta 45660 ttttatctat attgtattct actcctttct taatgcattt tataccgaat aagagatagc 45720 gaaggaattc tttttcggtg ccgctagtac ccttaatcat atcacatagt gttttatatt 45780 ccaaatttgt ggcaatagac ggtttatttc tatacgatag tttgtttctg gaatcctttg 45840 agtattctat accaatatta ttctttgatt cgaatttagt ttcttcgata ttagattttg 45900 tattacctat attcttgatg tagtactttg atgatttttc catggcccat tctattaagt 45960 cttccaagtt ggcatcatcc acatattgtg atagtaattc tcggatatca gtagcggcta 46020 ccgccattga tgtttgttca ttggatgagt aactactaat gtatacattt tccatttata 46080 acacttatgt attaactttg ttcatttata ttttttcatt attatgttga tattaacaaa 46140 agtgaatata tatatatgtt aataattgta ttgtggttat acggctacaa ttttataatg 46200 agtgaaagtc agtgtccgat gatcaatgac gatagcttta ctctgaaaag aaagtatcaa 46260 atcgatagtg cggagtcaac aataaaaatg gataagaaga ggataaagtt tcagaataga 46320 gccaaaatgg taaaagaaat aaatcagaca ataagagcag cacaaactca ttacgagaca 46380 ttgaaactag gatacataaa atttaagaga atgattagga ctactactct agaagatata 46440 gcaccatcta ttccaaataa tcagaaaact tataaactat tctcggacat ttcagccatc 46500 ggcaaagcat cacagaatcc gagtaagatg gtatatgctc tgctgcttta catgtttccc 46560 aatttgtttg gagatgatca tagattcatt cgttatagaa tgcatccaat gagtaaaatc 46620 aaacacaaga tcttctctcc tttcaaactt aatctttatta gaatattagt ggaagaaaga 46680 ttctataata atgaatgcag atctaataaa tggaaaataa ttggaacaca agttgataaa 46740 atgttgatag ctgaatctga taaatataca atagatgcaa ggtataacct aaaacccatg 46800 tatagaatca agggagaatc tgaagaagat accctcttta tcaaacagat ggtagaacaa 46860 tgtgtgacat cccaggaatt ggtggaaaaa gtgttgaaga tactgtttag agatttgttc 46920 aagagtggag aatacaaagc gtacagatac gatgatgatg tagaaaatgg atttatgga 46980 ttggatacac taaaattaaa cattgttcat gatatagttg aaccatgtat gcctgttcgt 47040 aggccagtgg ctaagatact gtgtaaagaa atggtaaata aatactttga gaatccgcta 47100 catattattg gtaaaaatct tcaagagtgc attgactttg ttagtgaata ggcatttcat 47160 ctttctccaa tactaattca aattgttaaa ttaataatgg atagtataaa tagttattag 47220 tgataaaata gtaaaaataa ttattagaat aagagtgtag tatcatagat aactctcttc 47280 tataaaaatg gattttattc gtagaaagta tcttatatac acagtagaaa ataatataga 47340 ttttttaaag gatgatacat taagtaaagt aaacaatttt accctcaatc atgtactagc 47400 tctcaagtat ctagttagca attttcctca acacgttatt actaaggatg tattagctaa 47460 taccaatttt tttgttttca tacatatggt acgatgttgt aaagtgtacg aagcggtttt 47520 acgacacgca tttgatgcac ccacgttgta cgttaaagca ttgactaaga attatttatc 47580 gtttagtaac gcaatacaat cgtacaagga aaccgtgcat aaactaacac aagatgaaaa 47640 atttttagag gttgccgaat acatggacga attaggagaa cttataggcg taaattatga 47700 cttagttctt aatccattat ttcacggagg ggaacccatc aaagatatgg aaatcatttt 47760 tttaaaactg tttaagaaaa cagacttcaa agttgttaaa aaattaagtg ttataagatt 47820 acttatttgg gcatacctaa gcaagaaaga tacaggcata gagtttgcgg ataatgatag 47880 acaagatata tatactctat ttcaacaaac tggtagaatc gtccatagca atctaacaga 47940 aacgtttaga gattatatct ttcccggaga taagactagc tattgggtgt ggttaaacga 48000 aagtatagct aatgatgcgg atatcgttct taatagacac gccattacca tgtatgataa 48060 aattcttagt tatatatact ctgagataaa acagggacgc gttaataaaa acatgcttaa 48120 gttagtttat atctttgagc ctgaaaaaga tatcagagaa cttctgctag aaatcatata 48180 tgatattcct ggagatatcc tatctattat tgatgcaaaa aacgacgatt ggaaaaaata 48240 ttttattagt ttttataaag ctaattttat taacggtaat acatttatta gtgatagaac 48300 gtttaacgag gacttattca gagttgttgt tcaaatagat cccgaatatt tcgataatga 48360 acgaattatg tctttattct ctacgagtgc tgcggacatt aaacgatttg atgagttaga 48420 tattaataac agttatatat ctaatataat ttatgaggtg aacgatatca cattagatac 48480 aatggatgat atgaagaagt gtcaaatctt taacgaggat acgtcgtatt atgttaagga 48540 atacaataca tacctgtttt tgcacgagtc ggatcccatg gtcatagaga acggaatact 48600 aaagaaactg tcatctataa aatccaagag tagacggctg aacttgttta gcaaaaacat 48660 tttaaaatat tatttagacg gacaattggc tcgtctaggt cttgtgttag atgattataa 48720 aggagacttg ttagttaaaa tgataaacca tcttaagtct gtggaggatg tatccgcatt 48780 cgttcgattt tctacagata aaaaccctag tattcttcca tcgctaatca aaactatttt 48840 agctagttat aatatttcca tcatcgtctt atttcaaagg tttttaagag ataatctata 48900 tcatgtagaa gaattcttgg ataaaagcat ccatctaacc aagacggata agaaatatat 48960 acttcaattg ataagacacg gtagatcata gaacagacca aatatattat taataatttg 49020 tatatacata gatataatta tcacatatta aaaattcaca catttttgat aaatgggaac 49080 tgctgcaaca attcagactc ccaccaaatt aatgaataaa gaaaatgcag aaatgatttt 49140 ggaaaaaatt gttgatcata tagttatgta tattagtgac gaatcaagtg attcagaaaa 49200 taatcctgaa tatattgatt ttcgtaacag atacgaagac tatagatctc tcattataaa 49260 aagtgatcac gagtttgtaa agctatgtaa aaatcatgca gagaaaagtt ctccagaaac 49320 gcaacaaatg attatcaaac acatatacga acaatatctt attccagtat ctgaagtact 49380 attaaaacct ataatgtcca tgggtgacat aattacatat aacggatgta aagacaatga 49440 atggatgcta gaacaactct ctaccctaaa ctttaacaat ctccgcacat ggaactcatg 49500 tagcataggc aatgtaacgc gtctgtttta tacatttttt agttatctga tgaaagataa 49560 actaaatata taagtataat cccattctaa tactttaacc tgatgtatta gcatcttatt 49620 agaatattaa cctaactaaa agacataaca taaaaactca ttacatagtt gataaaaagc 49680 ggtaggatat aaatattatg gctgccaccg ttccgcgttt tgacgacgtg tacaaaaatg 49740 cacaaagaag aattctagat caagaaacat tttttagtag aggtctaagt agaccgttaa 49800 tgaaaaacac atatctattt gataattacg cgtatggatg gataccagaa actgcaattt 49860 ggagtagtag atacgcaaac ttagatgcaa gtgactatta tcccatttcg ttgggattac 49920 ttaaaaagtt cgagtttctc atgtctctat ataaaggtcc tattccagta tacgaagaaa 49980 aagtaaatac tgaattcatt gctaatggat cgttctctgg tagatacgta tcatatcttc 50040 gaaagttttc tgctcttcca acaaacgagt ttattagttt tttgttactg acttccattc 50100 caatctataa tatcttgttc tggtttaaaa atactcagtt tgatattact aaacacacat 50160 tattcagata cgtctataca gataatgcca aacacctggc gttggctagg tatatgcatc 50220 aaacaggaga ctataagcct ttgtttagtc gtctcaaaga gaattatata tttaccggtc 50280 ccgttccaat aggtatcaaa gatataaatc accctaatct tagtagagca agaagtccat 50340 ccgattatga gacattagct aatattagta ctatattgta ctttaccaag tatgatccgg 50400 tattaatgtt tttatgttt tacgtacctg ggtattcaat tactacaaaa attactccag 50460 ccgtagaata tctaatggat aaactgaatc taacaaagag cgacgtacaa ctgttgtaaa 50520 ttattttatg cttcgtaaaa tgtaggtttt gaaccaaaca ttctttcaaa gaatgagatg 50580 cataaaactt tattatccaa tagattgact atttcggacg tcaatcgttt aaagtaaact 50640 tcgtaaaata ttctttgatc actgccgagt ttaaaacttc tatcgataat tgtttcatat 50700 gttttaatat ttacaagttt tttggtccat ggtacattag ccggacaaat atatgcaaaa 50760 taatatcgtt ctccaagttc tatagtttct ggattatttt tattatattc agtaaccaaa 50820 tacatattag ggttatctgc ggatttataa tttgagtgat gcattcgact caacataaat 50880 aattctagag gagacgatct actatcaaat tcggatcgta aatctgtttc taaagaacgg 50940 agaatatcta tacatacctg attagaattc atccgtcctt cagacaacat ctcagacagt 51000 ctggtcttgt atgtcttaat catattctta tgaaacttgg aaacatctct tctagtttca 51060 ctagtacctt tattaattct ctcaggtaca gattttgaat tcgacgatgc cgagtatttc 51120 atcgttgtat atttcttctt cgattgcata atcagattct tatataccgc ctcaaactct 51180 attttaaaat tattaaacaa tactctatta ttaatcagtc gttctaactc ctttgctatt 51240 tctatggact tatctacatc ttgactgtct atctctgtaa acacggagtc ggtatctcca 51300 tacacgctac gaaaacgaaa tctgtaatct ataggcaacg atgttttcac aatcggatta 51360 atatctctat cgtccatata aaatggatta cttaatggat tggcaaaccg taacataccg 51420 ttagataact ctgctccatt tagtaccgat tctagataca agatcattct acgtcctatg 51480 gatgtgcaac tcttagccga agcgtatgag tatagagcac tatttctaaa tcccatcaga 51540 ccatatactg agttggctac tatcttgtac gtatattgca tggaatcata gatggccttt 51600 tcagttgaac tggtagcctg ttttaacatc tttttatatc tggctctctc tgccaaaaat 51660 gttcttaata gtctaggaat ggttccttct atcgatctat cgaaaattgc tatttcagag 51720 atgaggttcg gtagtctagg ttcacaatga accgtaatat atctaggagg tggatatttc 51780 tgaagcaaga gctgattatt tatttcttct tccaatctat tggtactaac aacgacaccg 51840 actaatgttt ccggagatag atttccaaag atacacacat taggatacag actgttataa 51900 tcaaagatta atacattatt actaaacatt ttttgttttg gagcaaatac cttaccgcct 51960 tcataaggaa acttttgttt tgtttctgat ctaactaaga tagttttagt ttccaacaat 52020 agctttaaca gtggaccctt gatgactgta ctcgctctat attcgaatac catggattga 52080 ggaagcacat atgttgacgc acccgcgtct gtttttgttt ctactccata atactcccac 52140 aaatactgac acaaacaagc atcatgaata cagtatctag ccatatctaa agctatgttt 52200 agattataat ccttatacat ctgagctaaa tcaacgtcat cctttccgaa agataattta 52260 tatgtatcat taggtaaagt aggacataat agtacgactt taaatccatt ttcccaaata 52320 tctttacgaa ttactttaca tataatatcc tcatcaacag tcacataatt acctgtggtt 52380 aaaacctttg caaatgcagc ggctttgcct ttcgcgtccg tagtatcgtc accgatgaac 52440 gtcatttctc taactcctct atttaatact ttacccatgc aactgaacgc gttcttggat 52500 atagaatcca atttgtacga atccaatttt tcagattttt gaatgaatga atatagatcg 52560 aaaaatatag ttccattatt gttattaacg tgaaacgtag tattggccat gccgcctact 52620 cccttatgac tagactgatt tctctcataa atacagat gtacagcttc ctttttgtcc 52680 ggagatctaa agataatctt ctctcctgtt aataactcta gacgattagt aatatatctc 52740 agatcaaagt tatgtccgtt aaaggtaacg acatagtcga acgttagttc caacaattgt 52800 ttagctattc gtaacaaaac tatttcagaa cataaaacta gttctcgttc gtaatccatt 52860 tccattagtg actgtatcct caaacatcct ctatcgacgg cttcttgtat ttcctgttcc 52920 gttaacatct cttcattaat gagcgtaaac aataatcgtt taccacttaa atcgatataa 52980 cagtaacttg tatgcgagat tgggttaata aatacagaag gaaacttctt atcgaagtga 53040 cactctatat ctagaaataa gtacgatctt gggatatcga atctaggtat ttttttagcg 53100 aaacagttac gtggatcgtc acaatgataa catccattgt taatctttgt caaatattgc 53160 tcgtccaacg agtaacatcc gtctggagat atcccgttag aaatataaaa ccaactaata 53220 ttgagaaatt catccatggt ggcattttgt atgctgcgtt tctttggctc ttctatcaac 53280 cacatatctg cgacggagca ttttctatct ttaatatcta gattataact tattgtctcg 53340 tcaatgtcta tagttctcat ctttcccaac ggcctcgcat taaatggagg aggagacaat 53400 gactgatata tttcgtccgt cactacgtaa taaaagtaat gaggaaatcg tataaatacg 53460 gtctcaccat ttcgacatct ggatttcaga tataaaaatc tgttttcacc gtgactttca 53520 aaccaattaa tgcaccgaac atccatttat agaatttaga aatatatttt catttaaatg 53580 aatcccaaac attggggaag agccgtatgg accattattt ttatagtact ttcgcaagcg 53640 ggtttagacg gcaacataga agcgtgtaaa cgaaaactat atactatagt tagcactctt 53700 ccatgtcctg catgtagacg gcacgcgact atcgctatag aggacaataa tgtcatgtct 53760 agcgatgatc tgaattatat ttattatttt ttcatcagat tatttaacaa tttggcatct 53820 gatcccaaat acgcgatcga tgtgacaaag gttaaccctt tataaactta acccattata 53880 aaacttatga ttagtcacga ctgaaataac cgcgtgatta ttttttggta taattctaca 53940 cggcatggtt tctgtgacta tgaattcaac ccccgttaca ttagtgaaat ctttaacaaa 54000 cagcaagggt tcgtcaaaga cataaaactc attgtttaca atcgaaatag accccctatc 54060 acacttaaaa taaaaaatat ccttatcctt taccaccaaa taaaattctg attggtcaat 54120 gtgaatgtat tcacttaaca gttccacaaa tttattatt aactccgagg cacatacatc 54180 gtcggtattt tttatggcaa actttactct tccagcatcc gtttctaaaa aaatattaac 54240 gagttccatt tatatcatcc aatattattg aaatgacgtt gatggacaaa tgatacaaat 54300 aagaaggtac ggtacctttg tccaccatct ccctccaattc atgctctatt ttgtcattaa 54360 ctttaatgta tgaaaacagt acgccacatg cttccatgac agtgtgtaac actttggata 54420 caaaatgttt gacattagta taattgttca agactgtcaa tctataatag atagtagcta 54480 taatatattc tatgatggta ttgaagaaga tgacaacctt ggcatattga tcatttaaca 54540 cagacatggt atcaacagat agcttgaatg aaagagaatc agtaattgga ataagcgtct 54600 tctcgatgga gtgtccgtat accaacatgt ctgatatttt gatgtattcc attaaattat 54660 ttagtttttt cttttttc tcgttaaaca gcatttctgt caacggaccc caacatcgtt 54720 gaccgattaa gttttgattg atttttccgt gtaaggcgta tctagtcaga tcgtatagcc 54780 tatccaataa tccatcgtct gtgcgtagat cacatcgtac actttttaat tctctataga 54840 agagcgacag acatctggag caattacaga cagcaatttc tttatctct acagatgtaa 54900 gatacttgaa gacattccta tgatgatgca gaattttgga taacacggta ttgatggtat 54960 ctgttaccat aattcctttg atggctgata gtgtcagagc acaagatttc caatctttga 55020 caatttttag caccattatc tttgttttga tatctatatc agacagcatg gtgcgtctga 55080 caacacaagg attaagacgg aaagatgaaa tgattctctc aacatcttca atggatacct 55140 tgctattttt tctggcatta tctatatggg cgagaatatc ctctagagaa tcagtatcct 55200 ttttgatgat agtggatctc aatgacatgg gacgtctaaa ccttcttatt ctatcaccag 55260 attgcatggt gatttgtctt ctttctttta tcataatgta atctctaaat tcatcggcaa 55320 attgtctata tctaaaatca taatatgaga tgtttacctc tacaaatatc tgttcgtcca 55380 atgttagagt atttacatca gttttgtatt ccaaattaaa catggcaacg gatttaattt 55440 tatattcctc tattaagtcc tcgtcgataa taacagaatg tagataatca tttaatccat 55500 cgtacatggt tggaagatgc tcgttgacaa aatctttaat tgtcttgatg aaggtgggac 55560 tatatctaac atcttgatta ataaaattta taacattgtc cataggatac tttgtaacta 55620 gttttataca catctcttca tcggtaagtt tagacagaat atcgtgaaca ggtggtatat 55680 tatattcatc agatatacga agaacaatgt ccaaatctat attgtttaat atattatata 55740 gatgtagtgt agctcctaca ggaatatctt taactaagtc aatgatttca tcaaccgtta 55800 gatctatttt aaagttaatc atataggcat tgatttttaa aaggtatgta gccttgacta 55860 cattctcatt aattaaccat tccaagtcac tgtgtgtaag aagattatat tctatcataa 55920 gcttgactac atttggtccc gataccatta aagaattctt atgatataag gaaacagatt 55980 ttaggtactc atctactcta caagaatttt ggagagcctt aacgatatca gtgacgttta 56040 ttatttcagg agggaaaaaac ctaacattga gaatatcgga attaatagct tccagataca 56100 gtgattttgg caatagtccg tgtaatccat aatccagtaa cacgagctgg tgcttgctag 56160 acaccttttc aatgtttaat ttttttgaaa taagctttga taaagccttc ctcgcaaatt 56220 ccggatacat gaacatgtcg gcgacatgat taagtattgt tttttcatta tttttatatt 56280 ttctcaacaa gttctcaata ccccaataga tgatagaata tcacccaatg cgtccatgtt 56340 gtctatttcc aacaggtcgc tatatccacc aatagaagtt ttcccaaaaa agattctagg 56400 aacagttcta ccaccagtaa tttgttcaaa atagtcacgc aattcatttt cgggtttaaa 56460 ttctttaata tcgacaattt catacgctcc tcttttgaaa ctaaacttat ttagaatatc 56520 cagtgcattt ctacaaaaag gacatgtata cttgacaaaa attgtcactt tgttatggc 56580 caacctttgt tgtacaaatt cctcggccat tttaatattt aagtgatata aaactatctc 56640 gacttattta actctttagt cgagatatat ggacgcagat agctatatga tagccaacta 56700 cagaaggcaa acgctataaa aaacataatt acgacgagca tatttataaa tatttttatt 56760 cagcattact tgatatagta atattaggca cagtcaaaca ttcaaccact ctcgatacat 56820 taactctctc atttcttta acaaattctg caatatcttc gtaaaaagat tcttgaaact 56880 ttttagaata tctatcgact ctagatgaaa tagcgttcgt caacacata tgttttgtat 56940 acataaaggc gcccatttta acagtttcta gtgacaaaat gctagcgatc ctaggatcct 57000 ttagaatcac atagatgac gattcgtctc tcttagtaac tctagtaaaa taatcataca 57060 atctagtacg cgaaataata ttatccttga cttgaggaga tctaaacaat ctagttttga 57120 gaacatcgat aagttcatcg ggaatgacat acatactatc tttaatagaa ctcttttcat 57180 ccagttgaat ggattcgtcc ttaaccaact gattaatgag atcttctatt ttatcatttt 57240 ccagatgata tgtatgtcca ttaaagttaa attgtgtagc gcttcttttt agtctagcag 57300 ccaatacttt aacatcacta atatcgatat acaaaggaga tgatttatct atggtattaa 57360 gaattcgttt ttcgacatct gtcaaaacca attccttttt gcctgtatca tccagttttc 57420 catcctttgt aaagaaatta ttttctacta gactattaat aagactgata aggattcctc 57480 cataattgca caatccaaac tttttcacaa aactagactt tacaagatct acaggaatgc 57540 gtacttcagg tttcttagct tgtgattttt tcttttgtgg acattttctt gtgaccaact 57600 catctaccat ttcattgatt ttagcagtga aataagcttt caatgcacgg gcactgatac 57660 tattgaaaac gagttgatct tcaaattccg ccatttaagt tcaccaaaca acttttaaat 57720 acaaatatat caatagtagt agaataagaa ctataaaaaa aataataatt aaccaatacc 57780 aaccccaaca accggtatta ttagttgatg tgactgtttt ctcatcactt agaacagatt 57840 taacaatttc tataaagtct gtcaaatcat cttccggaga ccccataaat acaccaaata 57900 tagcggcgta caacttatcc atttatacat tgaatattgg cttttcttta tcgctatctt 57960 catcatattc atcatcaata tcaacaagtc ccagattacg agccagatct tcttctacat 58020 tttcagtcat tgatacacgt tcactatctc cagagagtcc gataacgtta gccaccactt 58080 ctctatcaat gattagtttc ttgagtgcga atgtaatttt tgtttccgtt ccggatctat 58140 agaaaactac aggtgtgata attgccttgg ccaattgtct ttctctttta ctgagtgatt 58200 ctagttcacc ttctatagat ctgagaatgg atgattctcc agtcgaaaca tattctacca 58260 tggctccgtt taatttgttg atgaagatgg attcatcctt aaatgttttc tctgtaatag 58320 tttccaccga aagactatgc aaagaatttg gaatgcgttc cttgtgctta atgtttccat 58380 agacggcttc tagaagttga tacaacatag gactagccgc ggtaactttt atttttagaa 58440 agtatccatc gcttctatct tgtttagatt tatttttata aagtttagtc tctccttcca 58500 acataataaa agtggaagtc atttgactag ataaactatc agtaagtttt atagagatag 58560 acgaacaatt agcgtattga gaagcattta gtgtaacgta ttcgatacat tttgcattag 58620 atttactaat cgattttgca tactctataa cacccgcaca agtctgtaga gaatcgctag 58680 atgcagtagg tcttggtgaa gtttcaactc tcttcttgat taccttaactc atgattaaac 58740 ctaaataatt gtactttgta atataatgat atatattttc actttatctc atttgagaat 58800 aaaaatgttt ttgtttaacc actgcatgat gtacagattt cggaatcaca aaccaccggt 58860 ggtttattt tatccttgtc caatgtgaat tgaatgggag cggatgcggg tttcgtacgt 58920 agatagtaca ttcccgtttt tagaccgaga ctccatccgt aaaaatgcat actcgttagt 58980 ttggaataac tcggatctgc tatatggata ttcatagatt gactttgatc gatgaaggct 59040 cccctgtctg cagccatttt tatgatcgtc ttttgtggaa tttcccaaat agttttataa 59100 actcgcttaa tatcttctgg aaggtttgta ttctgaatgg atccaccatc tgccataatc 59160 ctattcttga tctcatcatt ccataatttt ctctcggtta aaactctaag gagatgcgga 59220 ttaactactt gaaattctcc agacaatact ctccgagtgt aaatattact ggtatacggt 59280 tccaccgact cattatttcc caaaatttga gcagttgatg cagtcggcat aggtgccacc 59340 aataaactat ttctaagacc gtatgttctg attttatctt ttagaggttc ccaattccaa 59400 agatccgacg gtacaacatt ccaaagatca tattgtagaa taccgttact ggcgtacgat 59460 cctacatatg tatcgtatgg tccttccttc tcagctagtt cacaactcgc ctctaatgca 59520 ccgtaataaa tggtttcgaa gatcttctta tttagatctt gtgcttccag gctatcaaat 59580 ggataattta agagaataaa cgcgtccgct aatccttgaa caccaatacc gataggtcta 59640 tgtctcttat tagagatttc agcttctgga ataggataat aattaatatc tataatttta 59700 ttgagatttc tgacaattac tttgaccaca tccttcagtt tgagaaaatc aaatcgccca 59760 tctattacaa acatgttcaa ggcaacagat gccagattac aaacggctac ctcattagca 59820 tccgcatatt gtattatctc agtgcaaaga ttactacact tgatagttcc taaattttgt 59880 tgattactct ttttgttaca cgcatcctta taaagaatga atggagtacc agtttcaatc 59940 tgagattcta taatcgcttt ccagacgact cgagccttta ttatagattt gtatctcctt 60000 tctctttcgt atagtgtata caatcgttcg aactcgtctc cccaaacatt gtccaatcca 60060 ggacattcat ccggacacat caacgaccac tctccgtcat ccttcactcg tttcataaag 60120 agatcaggaa tccaaagagc tataaataga tctctggttc tatgttcctc gtttcctgta 60180 ttctttttaa gatcgaggaa cgccataata tcagaatgcc acggttccaa gtatatggcc 60240 ataactccag gccgtttgtt tcctccctga tctatgtatc tagcggtgtt attataaact 60300 ctcaacattg gaataatacc gtttgatata ccattggtac cggagatata gcttccactg 60360 gcacgaatat tactaattga tagacctatt ccccctgcca ttttagagat taatgcgcat 60420 cgttttaacg tgtcatagat accctctatg ctatcatcga tcatgttaag tagaaaacag 60480 ctagacattt ggtgacgact agttcccgca ttaaataagg taggagaagc gtgcgtaaac 60540 catttttcag aaagtagatt gtacgtctca atagctgagt ctatatccca ttgatgaatt 60600 cctactgcga cacgcattaa catgtgctga ggtctttcaa cgatcttgtt gtttattttc 60660 aacaagtagg atttttccaa agttttaaaa ccaaaatagt tgtatgaaaa gtctcgttcg 60720 taaataataa ccgagttgag tttatcctta tatttgttaa ctatatccat ggtgatactt 60780 gaaataatcg gagaatgttt cccattttta ggattaacat agttgaataa atcctccatc 60840 acttcactaa atagtttttt tgtttccttg tgtagatttg atacggctat tctggcggct 60900 agaatggcat aatccggatg ttgtgtagta caagtggctg ctatttcggc tgccagagtg 60960 tccaattcta ccgttgttac tccattatat attccttgaa taaccttcat agctatttta 61020 ataggatcta tatgatccgt gtttaagcca taacataatt ttctaatacg agacgtgatt 61080 ttatcaaaca tgacattttc cttgtatcca tttcgtttaa tgacaaacat ttttgttggt 61140 gtaataaaaa aattatttaa cttttcatta atagggattt gacgtacgta gcgtacaaaa 61200 tgattgttcc tggtatatag ataaagagtc ctatatattt gaaaatcgtt acggctcgat 61260 taaactttaa tgattgcata gtgaatatat cattaggatt taactccttg actatcaggg 61320 cggcaccaga aattaccatc aaaagcatta atacagttat gcctatcgca gttagaacgg 61380 ttatagcatc caccatttat atctaaaaat tagatcaaag aatatgtgac aaagtcctag 61440 ttgtatattg agaattgaca aaacaatgtt tcttacatat ttttttttta ttagtaaccg 61500 acttaatagt aggaactgga aaactagact tgattattct ataagtatag atacccttcc 61560 aaataatatt ctctttgata aaagttccag aaaatgtaga attttttaaa aagttatctt 61620 ttgctattac caagattgtg tttagacgct tattattaat atgagtgatg aaatccacac 61680 cgcctctaga tatcgccttt atttccacat tagatggtaa atccaatagt gaaactatct 61740 ttttaggaat gtatggactc gcgtttagag gagtgaacgt cttgggcgtc ggaaaggatg 61800 attcgtcaaa cgaataaaca atttcacaaa tggatgttaa tgtatagta ggaaattttt 61860 tgacgctagt ggaattgaag attctaatgg atgatgttct acctatttca tccgataaca 61920 tgttaatttc cgacaccaac ggttttaata tttcgatgat atacggtagt ctctctttcg 61980 gacttatata gcttattcca caatacgagt cattatatac tccaaaaaac aaaataacta 62040 gtataaaatc tgtatcgaat gggaaaaacg aaattatcga cataggtata gaatccggaa 62100 cattgaacgt attaatactt aattcttttt ctgtggtaag taccgatagg ttattgacat 62160 tgtatggttt taaatattct ataacttgag acttgataga tattagtgat gaattgaaaa 62220 ttatttttat caccacgtgt gtttcaggat catcgtcgac gcccgtcaac caaccgaatg 62280 gagtaaaata aatatcatta atatatgctc taaatattag tatttttatt aatcctttga 62340 ttatcatctt ctcgtacgcg aatgattcca tgatcaagag tgatttgaga acatcctccg 62400 gagtattaat gggcttagta aacagtacat cgttgcaata ataaaagtta tccaagttaa 62460 aggatattat gcattcgttt aaagatatca cctcatctga cggagacaat tttttggtag 62520 gttttagaga ctttgaagct acttgtttaa caaagttat catcgtcgtt tactattcta 62580 tttaattttg tagttaattt atcacatatc acattaattg actttttggt ccacttttcc 62640 atacgtttat attcttttaa tcctgcgtta tccgtttccg ttatatccag tgatagatcg 62700 tgcaggttaa atagaatgct cttaaataat gtcattttct tatccgctaa aaatttaaag 62760 aatgtataaa cctttttcag agatttgaaa ctcttaggtg gtgtcctagt acacaatatc 62820 ataaacaaac taataaacat tccacattca gattccaaca gctgattaac ttctacatta 62880 atacagccta ttttcgctcc aaatgtacat tcgaaaaatc tgaataaaac atcgatgtca 62940 caatttgtat tatccaatac agaatgtctg tgattcgtgt taaaaccatc ggagaaggaa 63000 tagaaataaa aattattata gtggtggaat tcagttggaa tattgcctcc ggaggtcataa 63060 aaggatacta aacattgttt tttatcataa attacacat tccaatgaga caaataacaa 63120 aatccaaaca ttacaaatct agaggtagaa cttttaattt tgtctttaag tatatacgat 63180 aagatatgtt tattcataaa cgcgtcaaat ttttcatgaa tcgctaagga gtttaagaat 63240 ctcatgtcaa attgtcctat ataatccact tcggatccat aagcaaactg agagactaag 63300 ttcttaatac ttcgattgct catccaggct cctctctcag gctctatttt catcttgacg 63360 acctttggat tttcaccagt atgtattcct ttacgtgata aatcatcgat tttcaaatcc 63420 atttgtgaga agtctatcgc cttagatact ttttcccgta gtcgaggttt aaagaaatac 63480 gctaacggta tactagtagg taactcaaag acatcatata tagaatggta acgcgtcttt 63540 aactcgtcgg ttaactcttt cttttgatcg agttcgtcgc tactattggg tctgctcagg 63600 tgccccaact ctactagttc caacatcata ccgataggaa tacaagacac tttgccagcg 63660 gttgtagatt tatcatattt ctccactaca tatccgttac aatttgttaa aaatttagat 63720 acatctatat tgctacataa tccagctagt gaatatatat gacataataa attggtaaat 63780 cctagttctg gtatttact aattactaaa tctgtatatc tttccattta tcatggaaaa 63840 gaatttacca gatatcttct tttttccaaa ctgcgttaat gtattctctt acaaatattc 63900 acaagatgaa ttcagtaata tgagtaaaac ggaacgtgat agtttctcat tggccgtgtt 63960 tccagttata aaacatagat ggcataacgc acacgttgta aaacataaag gaatatacaa 64020 agttagtaca gaagcacgtg gaaaaaaagt atctcctcca tcactaggaa aacccgcaca 64080 cataaaccta accgcgaagc aatatatata cagtgaacac acaataagct ttgaatgtta 64140 tagtttcta aaatgtataa caaatacaga aatcaattcg ttcgatgagt atatattaag 64200 aggactatta gaagctggta atagtttaca gatattttcc aattccgtag gtaaacgaac 64260 agatactata ggtgtactag ggaataagta tccatttagc aaaattccat tggcctcatt 64320 aactcctaaa gcacaacgag agatattttc agcgtggatt tctcatagac ctgtagtttt 64380 aactggagga actggagtgg gtaagacgtc acaggtaccc aagttattgc tttggtttaa 64440 ttatttattt ggtggattct ctactctaga taaaatcact aactttcacg aaagaccagt 64500 cattctatct cttcctagga tagctttagt tagattgcat agcaatacca ttttaaaatc 64560 attgggattt aaggtactag atggatctcc tatttcttta cggtacggat ctataccgga 64620 agaattaata aacaaacaac caaaaaaata tggaattgta ttttctaccc ataagttatc 64680 tctaacaaaa ctatttagtt atggcactct tattatagac gaagttcatg agcatgatca 64740 aataggagat attattatag cagtagcgag aaagcatcat acgaaaatag attctatgtt 64800 tttaatgact gccacgttag aggatgaccg agaacggcta aaagtatttt tacctaatcc 64860 cgcatttata catattcctg gagatacact gtttaaaatt agcgaggtat ttattcataa 64920 taagataaat ccatcttcca gaatggcata catagaagaa gaaaagagaa atttagttac 64980 tgctatacag atgtatactc ctcctgatgg atcatccggt atagtctttg tggcatccgt 65040 tgcacagtgt cacgaatata aatcatattt agaaaaaaga ttaccgtatg atatgtatat 65100 tattcatggt aaggtcttag atatagacga aatattagaa aaagtgtatt catcacctaa 65160 tgtatcgata attatttcta ctccttattt ggaatccagc gttactatac gcaatgttac 65220 acacatttat gatatgggta aagtttttgt ccccgctcct tttggaggat cgcaagaatt 65280 tatttctaaa tctatgagag atcaacgaaa aggaagagta ggaagagtta atcctggtac 65340 atacgtctat ttctatgatc tgtcttatat gaagtctata cagcgaatag attcagaatt 65400 tctacataat tatatattgt acgctaataa gtttaatcta acactccccg aagatttgtt 65460 tataatccct acaaatttgg atattctatg gcgtacaaag gaatatatag actcgttcga 65520 tattagtaca gaaacatgga ataaattatt atccaattat tatatgaaga tgatagagta 65580 tgctaaactt tatgtactaa gtcctattct cgctgaggag ttggataact ttgagaggac 65640 gggagaatta actagtattg tacgagaagc cattttatct ctaaatttac gaattaagat 65700 tttaaatttt aaacataaag atgatgatac gtatatacac ttttgtaaaa tattattcgg 65760 tgtctataac ggaacaaacg ctactatata ttatcataga cctctaacgg gatatatgaa 65820 tatgatttca gatactatat ttgttcctgt agataataac taaaaatcaa actctaatga 65880 ccacatcttt ttttagagat gaaaaatttt ccacatctcc ttttgtagac acgactaaac 65940 attttgcaga aaaaagttta ttagtgttta gataatcgta tacttcatca gtgtagatag 66000 taaatgtgaa cagataaaag gtattcttgc tcaatagatt ggtaaattcc atagaatata 66060 ttaatccttt cttcttgaga tcccacatca tttcaaccag agacgtttta tccaatgatt 66120 tacctcgtac tataccacat acaaaactag attttgcagt gacgtcgtac ctggtattcc 66180 taccaaacaa aattttactt ttagttcttt tagaaaattc taaggtagaa tctctatttg 66240 ccaatatgtc atctatgggaa ttaccactag caaaaaatga tagaaatata tattgataca 66300 tcgcagctgg ttttgatcta ctatacttta aaaacgaatc agattccata attgcctgta 66360 tatcatcagc tgaaaaacta tgttttacac gtattccttc ggcatttctt tttaatgata 66420 tatcttgttt agacaatgat aaagttatca tgtccatgag agacgcgtct ccgtatcgta 66480 taaatatttc attagatgtt agacgcttca ttaggggtat acttctataa ggtttcttaa 66540 ttagtccatc atttgttgcg tcaagaacta ctatcggatg ttgttgggta tctctagtgt 66600 tacacatggc cttactaaag tttgggtaaa taactatgat atctctatta attatagatg 66660 catatatttc atttgtcaag gatattagta tcgacttgct atcgtcatta atacgtgtaa 66720 tgtaatcata taaatcatgc gatagccaag gaaaattcaa atagatgttc atcatataat 66780 cgtcgctata attcatatta atactttgac attgactaat ttgtaatata gcctcgccac 66840 gaagaaagct ctcgtattca gtttcatcga taaaggatac cgttaaatat aactggttgc 66900 cgatagtctc atagtctatt aagtggtaag tttcgtacaa atacagaatc cctaaaatat 66960 tatctaatgt tggattaatc tttaccataa ctgtataaaa tggagacgga gtcataacta 67020 ttttaccgtt tgtacttact ggaatagacg aaggaataat ctccggacat gctggtaaag 67080 acccaaatgt ctgtttgaag aaatccaatg ttccaggtcc taatctctta acaaaaatta 67140 cgatattcga tcccgatatc ctttgcattc tatttaccag catatcacga actatattaa 67200 gattatctat catgtctatt ctcccaccgt tatataaatc gcctccgcta agaaacgtta 67260 gtatatccat acaatggaat acttcatttc taaaatagta ttcgttttct aattctttaa 67320 tgtgaaatcg tatactagaa agggaaaaat tatctttgag ttttccgtta gaaaagaacc 67380 acgaaactaa tgttctgatt gcgtccgatt ccgttgctga attaatggat ttacaccaaa 67440 aactcatata acttctagat gtagaagcat tcgctaaaaa attagtagaa tcaaaggata 67500 taagtagatg ttccaacaag tgagcaattc ccaagatttc atctatatca ttctcgaatc 67560 cgaaattaga aattcccaag tagatatcct ttttcatccg atcgttgatg aaaatacgaa 67620 ctttattcgg taagacaatc atttactaag gagtaaaata ggaagtaatg ttcgtatgtc 67680 gttatcatcg tataaattaa aggtgtgttt tttaccatta agtgacatta taattttacc 67740 aatattggaa ttataatata ggtgtatttg cgcactcgcg acggttgatg catcggtaaa 67800 tatagctgta tctaatgttc tagtcggtat ttcatcattt cgctgtctaa taatagcgtt 67860 ttctctatct gtttccatta cagctgcctg aagtttatg gtcggataat atgtaaaata 67920 ataagaaata catacgaata acaaaaataa aataagatat aataaagatg ccatttagag 67980 atctaatttt gtttaacttg tccaaattcc tacttacaga agatgaggaa tcgttggaga 68040 tagtgtcttc cttatgtaga ggatttgaaa tatcttatga tgacttgata acttactttc 68100 cagataggaa ataccataaa tatatttcta aagtatttga acatgtagat ttatcggagg 68160 aattaagtat ggaattccat gatacaactc tgagagattt agtctatctt agattgtaca 68220 agtattccaa gtgtatacgg ccgtgttata aattaggaga taatctaaaa ggcatagttg 68280 ttataaagga caggaatatt tatattagag aagcaaatga tgacttgata gaatatctcc 68340 tcaaggaata cactcctcag atttatacat attctaatga gcgcgtcccc ataactggtt 68400 caaaattaat tctttgtgga ttttctcaag ttacatttat ggcgtataca acgtcgcata 68460 taacaacaaa taaaaaggta gatgttctcg tttccaaaaa atgtatagat gaactagtcg 68520 atccaataaa ttatcaaata cttcaaaatt tatttgataa aggaagcgga acaataaaca 68580 aaatactcag gaagatattt tattcggtaa ccggtggcca aactccataa tttgcttttt 68640 ctatttcgga ttttagaatt tccaaattca ccagcgattt atcggttttg gtgaaatcca 68700 aggatttatt aatgtccaca aatgccattt gttttgtctg tggattgtat ttgaaaatgg 68760 aaacgatgta gttagataga tgcgctgcaa agtttcctat tagggttccg cgctttacgt 68820 cacccagcat acttgaatca ccatccttta aaaaaaatga taagatatca acatggagta 68880 tatcatactc ggattttaat tcttctactg catcactgac attttcacaa atactacaat 68940 acggtttacc gaaaataatc agtacgttct tcatttatgg gtatcaaaaa cttaaaatcg 69000 ttactgctgg aaaataaatc actgacgata ttagatgata atttatacaa agtatacaat 69060 ggaatatttg tggatacaat gagtatttat atagccgtcg ccaattgtgt cagaaactta 69120 gaagagttaa ctacggtatt cataaaatac gtaaacggat gggtaaaaaa gggagggcat 69180 gtaacccttt ttatcgatag aggaagtata aaaattaaac aagacgttag agacaagaga 69240 cgtaaatatt ctaaattaac caaggacaga aaaatgctag aattagaaaa gtgtacatcc 69300 gaaatacaaa atgttaccgg atttatggaa gaagaaataa aggcagaaat gcaattaaaa 69360 atcgataaac tcacatttca aatatattta tctgattctg ataacataaa aatatcattg 69420 aatgagatac taacacattt caacaataat gagaatgtta cattatttta ttgtgatgaa 69480 cgagacgcag aattcgttat gtgtctcgag gctaaaacac atttctctac cacaggagaa 69540 tggccgttga taataagtac cgatcaggat actatgctat ttgcatctac tgataatcat 69600 cctaagatga taaaaaactt aactcaactg tttaaatttg ttccctcggc agaggataac 69660 tatttagcaa aattaacggc gttagtgaat ggatgtgatt tctttcctgg actctatggg 69720 gcatctataa cacccaccaa cttaaacaaa atacaattgt ttagtgattt tacaatcgat 69780 aatatagtca ctagtttggc aattaaaaat tattatagaa agactaactc taccgtagac 69840 gtgcgtaata ttgttacgtt tataaacgat tacgctaatt tagacgatgt ctactcgtat 69900 gttcctcctt gtcaatgcac tgttcaagaa tttatatttt ccgcattaga tgaaaaatgg 69960 aacaatttta aatcatctta tttagagacc gttccgttac cctgccaatt aatgtatgca 70020 ttagaaccac gcaaggat tgatgtttca gaagttaaaa ctttatcatc ttatatagat 70080 ttcgaaaata ctaaatcaga tatcgatgtt ataaaatcta tatcttcgat cttcggatat 70140 tctaacgaaa actgtaacac tatagtgttc ggcatctata aggataattt actactgagt 70200 ataaatagtt cattttactt taacgatagt ctgttaataa ccaatactaa aagtgataat 70260 ataataaata taggttacta gattaaaaat ggtgttccaa ctcgtgtgct ctacatgcgg 70320 caaagatatt tctcacgaac gatataaatt gattatacga aaaaaatcat taaaggatgt 70380 actcgtcagt gtaaagaacg aatgttgtag gttaaaatta tctacacaaa tagaacctca 70440 acgtaactta acagtgcaac ctctattgga tataaactaa tatggatccg gttaatttta 70500 tcaagacata tgcgcctaga ggttctatta tttttattaa ttataccatg tcattaacaa 70560 gtcatttgaa tccatcgata gaaaaacatg tgggtattta ttatggtacg ttattatcgg 70620 aacacttggt agttgaatct acctatagaa aaggagttcg aatagtccca ttggatagtt 70680 tttttgaagg atatcttagt gcaaaagtat acatgttaga gaatattcaa gttatgaaaa 70740 tagcagctga tacgtcatta actttatgg gtattccgta tggatttggt catgatagaa 70800 tgtattgttt taaattggta gctgaatgtt ataaaaatgc cggtattgat acatcgtcta 70860 aacgaatatt aggtaaagat atttttctga gccaaaactt cacagatgat aatagatgga 70920 taaagatata tgattctaat aatttaacat tttggcaaat tgattacctt aaagggtgag 70980 ttaatatgca taactactcc tccgttgttt tttccctcgt tctttttctt aacgttgttt 71040 gccatcactc tcataatgta aagatattct aaaatggtaa acttttgcat atcggacgca 71100 gaaattggta taaatgttgt aattgtatta tttcccgtca atggactagt cacagctcca 71160 tcagttttat atcctttaga gtatttctca ctcgtgtcta acattctaga gcattccatg 71220 atctgtttat cgttgatatt ggccggaaag atagattttt tattttttat tatattacta 71280 ttggcaattg tagatataac ttctggtaaa tatttttcta ccttttcaat ctcttctatt 71340 ttcaagccgg ctatatattc tgctatattg ttgctagtat caataccttt tctggctaag 71400 aagtcatatg tggtattcac tatatcagtt ttaactggta gttccattag cctttccact 71460 tctgcagaat aatcagaaat tggttcttta ccagaaaatc cagctactat aataggctca 71520 ccgatgatca ttggcaaaat cctatattgt accagattaa tgagagcata tttcatttcc 71580 aataattctg ctagttcttg agacattgat ttatttgatg aatctagttg gttctctaga 71640 tactctacca tttctgccgc atacaataac ttgttagata aaatcagggt tatcaaagtg 71700 tttagcgtgg ctagaatagt gggcttgcat gtattaaaga atgcggtagt atgagtaaac 71760 cgttttaacg aattatatag tctccagaaa tctgtggcgt tacatacatg agccgaatga 71820 catcgaagat tgtccaatat ttttaatagc tgctctttgt ccattatttc tatatttgac 71880 tcgcaacaat tgtagatacc attaatcacc gattcctttt tcgatgccgg acaatagcac 71940 aattgtttag ctttggactc tatgtattca gaattaatag atatatctct taatacagat 72000 tgcactatac attttgaaac tatgtcaaaa attgtagaac gacgctgttc tgcagccatt 72060 taactttaaa taatttacaa aaatttaaaa tgagcatccg tataaaaatc gataaactgc 72120 gccaaattgt ggcatatttt tcagagttca gtgaagaagt atctataaat gtagactcga 72180 cggatgagtt aatgtatatt tttgccgcct tgggcggatc tgtaaacatt tggggccatta 72240 tacctctcag tgcatcagtg ttctaccgcg gagccgaaaa cattgtgttt aatcttcctg 72300 tgtccaaggt aaaatcgtgt ttgtgtagtt ttcacaatga tgccatcata gatatagaac 72360 ctgatctgga aaataatcta gtaaaacttt ctagttatca tgtagtaagt gtcgattgta 72420 acaaggaact gatgcctatt aggacagata ctactatttg tctaagtata gatcaaaaga 72480 aatcttacgt gtttaatttt cacaagtatg aagaaaaatg ttgtggtaga accgtcattc 72540 atttagaatg gttgttgggc tttatcaagt gtattagtca gcatcagcat ttggctatta 72600 tgtttaaaga tgacaatatt attatgaaga ctcctggtaa tactgatgcg ttttccaggg 72660 aatattctat gactgaatgt tctcaagaac tacaaaagtt ttctttcaaa atagctatct 72720 cgtctctcaa caaactacga ggattcaaaa agagagtcaa tgtttttgaa actagaatcg 72780 taatggataa tgacgataac attctaggaa tgttgttttc ggatagagtt caatccttta 72840 agatcaacat ctttatgacg tttttagatt aatactttca atgagataaa tatgggtggc 72900 ggagtaagtg ttgagctccc taaacgggat ccgcctccgg gagtacccac tgatgagatg 72960 ttattaaacg tggataaaat gcatgacgtg atagctcccg ctaagctttt agaatatggg 73020 catataggac cactagcaaa agataaagag gataaagtaa agaaaagata tccagagttt 73080 agattagtca acacaggacc cggtggtctt tcggcattgt taagacaatc gtataatgga 73140 accgcaccca attgctgtcg cacttttaat cgtactcatt attggaagaa ggatggaaag 73200 atatcagata agtatgaaga gggtgcagta ttagaatcgt gttggccaga cgttcacgac 73260 accggaaaat gcgatgttga tttatcgac tggtgtcagg gggatacgtt cgatagaaac 73320 atatgccatc agtggatcgg ttcagccttt aataggagta atagaactgt agagggtcaa 73380 caatcgttaa taaatctgta taataagatg caaacattat gtagtaaaga tgctagtgta 73440 ccaatatgtg aatcattttt gcatcattta cgcgcacaca atacagaaga tagcaaagag 73500 atgatcgatt atattctaag acaacagtct gcggacttta aacagaaata tatgagatgt 73560 agttatccca ctagagataa gttagaagag tcattaaaat atgcggaacc tcgagaatgt 73620 tgggatccag agtgttcgaa tgccaatgtt aatttcttgc taacacgtaa ttataataat 73680 ttaggacttt gcaatattgt acgatgtaat actagcgtga acaacttaca gatggataaa 73740 acttcctcat taagattgtc atgtggatta agcaatagtg atagattttc tactgttccc 73800 gtcaatagag caaaagtagt tcaacataat attaaacact cgttcgacct aaaattgcat 73860 ttgatcagtt tattatctct cttggtaata tggatactaa ttgtagctat ttaaatgggt 73920 gccgcggcaa gcatacagac gacggtgaat acactcagcg aacgtatctc gtctaaatta 73980 gaacaagaag cgaatgctag tgctcaaaca aaatgtgata tagaaatcgg aaatttttat 74040 atccgacaaa accatggatg taacctcact gttaaaaata tgtgctctgc ggacgcggat 74100 gctcagttgg atgctgtgtt atcagccgct acagaaacat atagtggatt aacaccgggaa 74160 caaaaagcat acgtgccagc tatgtttact gctgcgttaa acattcagac gagtgtaaac 74220 actgttgtta gagattttga aaattatgtg aaacagactt gtaattctag cgcggtcgtc 74280 gataacaaat taaagataca aaacgtaatc atagatgaat gttacggagc cccaggatct 74340 ccaacaaatt tggaatttat taatacagga tctagcaaag gaaattgtgc cattaaggcg 74400 ttgatgcaat tgacgactaa ggccactact caaatagcac ctaaacaagt tgctggtaca 74460 ggagttcagt tttatatgat tgttatcggt gttataatat tggcagcgtt gtttatgtac 74520 tatgccaagc gtatgttgtt cacatccacc aatgataaaa tcaaacttat tttagccaat 74580 aaggaaaacg tccattggac tacttacatg gacacatct ttagaacttc tccgatggtt 74640 attgctacca cggatatgca aaactgaaaa tatattgata atattttaat agattaacat 74700 ggaagttatc actgatcgtc tagacgatat agtgaaacaa aatatagcgg atgaaaaatt 74760 tgtagatttt gttatacacg gtctagagca tcaatgtcct gctatacttc gaccattaat 74820 taggttgttt attgatatac tattatttgt tatagtaatt tatattttta cggtacgtct 74880 agtaagtaga aattatcaaa tgttgttggc gttggtggcg ctagtcatca cattaactat 74940 tttttattac tttatactat aatagtacta gactgacttc taacaaacat ctcacctgcc 75000 ataaataaat gcttgatatt aaagtcttct atttctaaca ctattccatc tgtggaaaat 75060 aatactctga cattatcgct aattgacaca tcggtgagtg atatgcctat aaagtaataa 75120 tcttctttgg gcacatatac cagtgtacca ggttctaaca acctatttac tggtgctcct 75180 atagcatact ttttctttac cttgagaata tccatcgttt gcttggtcaa tagcgatatg 75240 tgatttttta tcaaccactc gaaaaagtaa ttggagtgtt catatcctct acgggctatt 75300 gtctcatggc cgtgtatgaa atttaagtaa cacgactgtg gtagatttgt tctatagagc 75360 cggttgccgc aaatagatag aactaccaat atgtctgtac aaatgttaaa cattaattga 75420 ttaacagaaa aaacaatgtt cgttctggga atagaaacca gatcaaaaca aaattcgtta 75480 gaatatatgc cacgtttata cattgaatat aaaataacta cagtttgaaa aataacagta 75540 tcatttaaac atttaacttg cggggttaat ctcacaactt tactgttttt gaactgttca 75600 aaatatagca tagatccgtg agaaatacgt ttagccgcct ttaatagagg aaatcccacc 75660 gcctttctgg atctcaccaa cgacgatagt tctgaccagc aactcatttc ttcatcatcc 75720 acctgtttta acatataata ggcaggagat agatatccgt cattgcaata ttccttctcg 75780 taggcacaca atctaatatt gataaaatct ccattctctt ctctgcattt attatcttgt 75840 ttcggtggct gattaggctg tagtcttggt ttaggctttg gtatatcgtt gttgaatcta 75900 ttttggtcat taaatctttc atttcttcct ggtatatttt tatcacctcg tttggttgga 75960 tttttgtcta tattatcgtt tgtaacatcg gtacgggtat tcatttatca caaaaaaaac 76020 ttctctaaat gagtctactg ctagaaaacc tcatcgaaga agataccata ttttttgcag 76080 gaagtatatc tgagtatgat gatttacaaa tggtattgc cggcgcaaaa tccaaatttc 76140 caagatctat gctttctatt tttaatatag tacctagaac gatgtcaaaa tatgagttgg 76200 agttgattca taacgaaaat atcacaggag caatgtttac cacaatgtat aatataagaa 76260 acaatttggg tctaggagat gataaactaa ctattgaagc cattgaaaac tatttcttgg 76320 atcctaacaa tgaagttatg cctcttatta ttaataatac ggatatgact gccgtcattc 76380 ctaaaaaaag tggtaggaga aagaataaga acatggttat cttccgtcaa ggatcatcac 76440 ctatcttgtg tattttcgaa actcgtaaaa agattaatat ttataaagaa aatatggaat 76500 ccgcgtcgac tgagtataca cctatcggag acaacaaggc tttgatatct aaatatgcgg 76560 gaattaatgt cctgaatgtg tattctcctt ccacatccat gagattgaat gccatttacg 76620 gattcaccaa taaaaataaa ctagagaaac ttagtactaa taaggaacta gaatcgtata 76680 gttctagccc tcttcaagaa cccattaggt taaatgattt tctgggacta ttggaatgtg 76740 ttaaaaagaa tattcctcta acagatattc cgacaaagga ttgattacta taaatggaga 76800 atgttcctaa tgtatacttt aatcctgtgt ttatagagcc cacgtttaaa cattctttat 76860 taagtgttta taaacacaga ttaatagttt tatttgaagt attcgttgta ttcattctaa 76920 tatatgtatt ttttagatct gaattaaata tgttctttat gcctaaacga aaaatacccg 76980 atcctattga tagattacga cgtgctaatc tagcgtgtga agacgataaa ttaatgatct 77040 atggattacc atggatgaca actcaaacat ctgcgttatc aataaatagt aaaccgatag 77100 tgtataaaga ttgtgcaaag cttttgcgat caataaatgg atcacaacca gtatctctta 77160 acgatgttct tcgcagatga tgattcattt tttaagtatt tggctagtca agatgatgaa 77220 tcttcattat ctgatatatt gcaaatcact caatatctag actttctgtt attattattg 77280 atccaatcaa aaaataaatt agaagccgtg ggtcattgtt atgaatctct ttcagaggaa 77340 tacagacaat tgacaaaatt cacagacttt caagatttta aaaaactgtt taacaaggtc 77400 cctattgtta cagatggaag ggtcaaactt aataaaggat atttgttcga ctttgtgatt 77460 agtttgatgc gattcaaaaa agaatcctct ctagctacca ccgcaataga tcctattaga 77520 tacatagatc ctcgtcgtga tatcgcattt tctaacgtga tggatatatt aaagtcgaat 77580 aaagtgaaca ataattaatt ctttattgtc atcatgaacg gcggacatat tcagttgata 77640 atcggcccca tgttttcagg taaaagtaca gaattaatta gacgagttaa acgttatcaa 77700 atagctcaat ataaatgcgt gactataaaa tattctaacg ataatagata cggaacggga 77760 ctatggacgc atgataagaa taattttgaa gcattggaag caactaaact atgcgatgtt 77820 ttggaattaa ttacagattt ctccgtgata ggtatcgatg aaggacagtt ctttccagac 77880 attgttgaat tctgtgagcg tatggcaaac gaaggaaaaa tagttatagt agccgcactc 77940 gatgggacat ttcaacgtaa accgtttaat aatattttga atcttattcc attatctgaa 78000 atggtggtaa aactaactgc tgtgtgtatg aaatgcttta aggaggcttc cttttctaaa 78060 cgattgggtg agggaaaccga gataaaaata ataggaggta atgatatgta tcaatcggtg 78120 tgtagaaagt gttacatcga ctcataatat tatatttttt atctaaaaaa ctaaaaataa 78180 acattgatta aattttaata taatacttaa aaatggatgt tgtgtcgtta gataaaccgt 78240 ttatgtattt tgaggaaatt gataatgagt tagattacga accagaaagt gcaaatgagg 78300 tcgcaaaaaa actgccgtat caaggacagt taaaactatt actaggagaa ttattttttc 78360 ttagtaagtt acagcgacac ggtatattag atggtgccac cgtagtgtat ataggatctg 78420 ctcccggtac acatatacgt tatttgagag atcatttcta taatttagga gtgatcatca 78480 aatggatgct aattgacggc cgccatcatg atcctatttt aaatggattg cgtgatgtga 78540 ctctagtgac tcggttcgtt gatgaggaat atctacgatc catcaaaaaa caactgcatc 78600 cttctaagat tattttaatt tctgatgtga gatccaaacg aggaggaaat gaacctagta 78660 cggcggattt actaagtaat tacgctctac aaaatgtcat gattagtatt ttaaaccccg 78720 tggcgtctag tcttaaatgg agatgcccgt ttccagatca atggatcaag gacttttata 78780 tcccacacgg taataaaatg ttacaacctt ttgctccttc atattcagct gaaatgagat 78840 tattaagtat ttataccggt gagaacatga gactgactcg agttaccaaa ttagacgctg 78900 taaattatga aaaaaagatg tactacctta ataagatcgt ccgtaacaaa gtagttgtta 78960 actttgatta tcctaatcag gaatatgact attttcacat gtactttatg ctgaggaccg 79020 tgtactgcaa taaaacattt cctactacta aagcaaaggt actatttcta caacaatcta 79080 tatttcgttt cttaaatatt ccaacaacat caactgaaaa agttagtcat gaaccaatac 79140 aacgtaaaat atctagcaaa aattctatgt ctaaaaacag aaatagcaag agatccgtac 79200 gcggtaataa atagaaacgt gctactgaga tatactaccg atatagagta taatgattta 79260 gttactttaa taaccgttag acataaaatt gattctatga aaactgtgtt tcaggtattt 79320 aacgaatcat ccataaatta tactccggtt gatgatgatt atggagaacc aatcattata 79380 acatcgtatc ttcaaaaagg tcataacaag tttcctgtaa attttctata catagatggg 79440 gtaatatctg acttatttcc tagctttgtt agactagata ctacagaaac taatatagtt 79500 aatagtgtac tacaaacagg tgatggtaaa aagactcttc gtcttcccaa aatgttagag 79560 acggaaatag ttgtcaagat tctctatcgc cctaatatac cattaaaaat tgttagattt 79620 ttccgcaata acatggtaac tggagtagag atagccgata gatctgttat ttcagtcgct 79680 gattaatcaa ttagtagaga tgagataaga acattataat aatcaataat atatcttata 79740 tcttatatct tatatcttat atcttgttta gaaaaatgct aatattaaaa tagctaacgc 79800 tagtaatcca atcggaagcc atttgatatc tataataggg tatctaattt cctgatttaa 79860 atagcggaca gctatattct cggtagctac tcgtttggaa tcacaaacat tatttacatc 79920 taatttacta tctgtaatgg aaacgtttcc caatgaaatg gtacaatccg atacattgca 79980 ttttgttata ttttttttta aagaggctgg taacaacgca tcgcttcgtt tacatggctc 80040 gtaccaacaa taatagggta atcttgtatc tattcctatc cgtactatgc ttttatcagg 80100 ataaatacat ttacatcgta tatcgtcttt gttagcatca cagaatgcat aaatttgttc 80160 gtccgtcatg ataaaaattt aaagtgtaaa tataactatt atttttatag ttgtaataaa 80220 aagggaaatt tgattgtata ctttcggttc tttaaaagaa actgacttga taaaaatggc 80280 tgtaatctct aaggttacgt atagtctata tgatcaaaaa gagattaatg ctacagatat 80340 tatcattagt catgttaaaa atgacgacga tatcggtacc gttaaagatg gtagactagg 80400 tgctatggat ggggcattat gtaaaacttg tgggaaaacg gaattggaat gtttcggtca 80460 ctggggtaaa gtaagtattt ataaaactca tatagttaag cctgaattta tttcagaaat 80520 tattcgttta ctgaatcata tatgtattca ctgcggatta ttgcgttcac gagaaccgta 80580 ttccgacgat attaacctaa aagagttatc gggacacgct cttaggagat taaaggataa 80640 aatattatcc aagaaaaagt catgttggaa cagcgaatgt atgcaaccgt atcaaaaaat 80700 tactttttca aagaaaaagg tttgtttcgt caacaagttg gatgatatta acgttcctaa 80760 ttctctcatc tatcaaaagt taatttctat tcatgaaaag ttttggccat tattagaaat 80820 tcatcaatat ccagctaact tattttatac agactacttt cccatccctc cgctgattat 80880 tagaccggct attagttttt ggatagatag tatacccaaa gaaaccaatg aattaactta 80940 cttattaggt atgatcgtta agaattgtaa cttgaatgct gatgaacagg ttatccagaa 81000 ggcggtaata gaatacgatg atattaaaat tatttctaat aacactacca gtatcaattt 81060 atcatatatc acatccggca aaaataatat gattagaagt tatatcgtcg cccggcgaaa 81120 agatcagacc gctagatctg taattggtcc cagtacatct atcaccgtta atgaggtagg 81180 aatgcccgca tatattagaa atacacttac agaaaagata tttgttaatg cctttacagt 81240 ggataaagtt aaacaactat tagcgtcaaa ccaagttaaa ttttacttta ataaacgatt 81300 aaaccaatta acaagaatac gccaaggaaa gtttatcaaa aataaaatac atttatgcc 81360 tggtgattgg gtagaagtag ctgttcaaga atatacaagt attatttttg gaagacagcc 81420 gtctctacat agatacaacg tcatcgcttc atctatcaga gctaccgaag gagatactat 81480 caaaatatct cccggaattg ccaactctca aaatgctgat ttcgacgggg atgaggaatg 81540 gatgatatta gaacaaaatc ctaaagctgt aattgaacaa agtattctta tgtatccgac 81600 gacgttactc aaacacgata ttcatggagc ccccgtttat ggatctattc aagatgaaat 81660 cgtagcagcg tattcattgt ttaggataca agatctttgt ttagatgaag tattgaacat 81720 cttggggaaa tatggaagag agttcgatcc taaaggtaaa tgtaaattca gcggtaaaga 81780 tatctatact tacttgatag gtgaaaagat taattatccg ggtctcttaa aggatggtga 81840 aattattgca aacgacgtag atagtaattt tgttgtggct atgaggcatc tgtcattggc 81900 tggactctta tccgatcata agtcgaacgt ggaaggtatc aactttatta tcaagtcatc 81960 ttatgttttt aagagatatc tatctattta cggttttggg gtgacattca aagatctgag 82020 accaaattcg acgttcacta ataaattgga ggccatcaac gtagaaaaaa tagaacttat 82080 caaagaagca tacgccaaat atctcaacga tgtaagagac gggaaaatag ttccattatc 82140 taaagcttta gaggcggact atgtggaatc catgttatcc aacttgacaa atcttaatat 82200 ccgagagata gaagaacata tgagacaaac gctgatagat gatccagata ataacctcct 82260 gaaaatggcc aaagcgggtt ataaagtaaa tcctacagaa ctaatgtata ttctaggtac 82320 gtatggacaa caaaggattg atggtgaacc agcagagact cgagtattgg gtagagtctt 82380 accttactat cttccagact ctaaggatcc agaaggaaga ggttacattc ttaattcttt 82440 aacaaaagga ttaacgggtt ctcaatatta cttttcgatg ctggttgcaa gatctcaatc 82500 tactgatatc gtctgtgaaa catcacgtac cggaacactg gctagaaaaa tcattaaaaa 82560 gatggaggat atggtggtcg acggatacgg acaagtagtt ataggtaata cgctcatcaa 82620 gtacgccgcc aattatacca aaattctagg ctcagtatgt aaacctgtag atcttatcta 82680 tccagatgag tccatgactt ggtatttgga aattagtgct ctgtggaata aaataaaaca 82740 gggattcgtt tactctcaga aacagaaact tgcaaagaag acattggcgc cgtttaattt 82800 cctagtattc gtcaaaccca ccactgagga taatgctatt aaggttaagg atctgtacga 82860 tatgattcat aacgtcattg atgatgtgag agagaaatac ttctttacgg tatctaatat 82920 agattttatg gagtattat tcttgacgca tcttaatcct tctagaatta gaattacaaa 82980 agaaacggct atcactatct ttgaaaagtt ctatgaaaaa ctcaattata ctctaggtgg 83040 tggaactcct attggaatta tttctgcaca ggtattgtct gagaagttta cacaacaagc 83100 cctgtccagt tttcacacta ctgaaaaaag tggtgccgtc aaacaaaaac ttggtttcaa 83160 cgagtttaat aacttgacta atttgagtaa gaataagacc gaaattatca ctctggtatc 83220 cgatgatatc tctaaacttc aatctgttaa gattaatttc gaatttgtat gtttgggaga 83280 attaaatcca gacatcactc ttcgaaaaga aacagatagg tatgtagtag atataatagt 83340 caatagatta tacatcaaga gagcagaaat taccgaatta gtcgtcgaat atatgattga 83400 acgatttatc tcctttagcg tcattgtaaa ggaatggggt atggaaacat tcattgagga 83460 tgaggataat attagattta ctgtctacct aaatttcgtt gaaccggaag aattgaatct 83520 tagtaagttt atgatggttc ttccgggtgc cgccaacaag ggcaagatta gtaaattcaa 83580 gattcctatc tctgactata cgggatatga cgacttcaat caaacaaaaa agctcaataa 83640 gatgactgta gaactcatga atctaaaaga attgggttct ttcgatttgg aaaacgtcaa 83700 cgtgtatcct ggaggtatgga atacatacga tatcttcggt atcgaggccg ctcgtgaata 83760 cttgtgcgaa gccatgttaa acacctatgg agaagggttc gattatctgt atcagccttg 83820 tgatcttctc gctagtttac tatgtgctag ttacgaacca gaatcagtga ataaattcaa 83880 gttcggcgca gctagtactc ttaagagagc tacgttcgga gacaataaag cattgttaaa 83940 cgcggctctt cataaaaagt cagaacctat taacgataat agtagctgcc acttttttag 84000 caaggtccct aatataggaa ctggatatta caaatacttt atcgacttgg gtcttctcat 84060 gagaatggaa aggaaactat ctgataagat atcttctcaa aagatcaagg aaatggaaga 84120 aacagaagac ttttaattct tatcaataac atatttttct atgatctgtc ttttaaacga 84180 tggattttcc acaaatgcgc ctctcaagtc cctcatagaa tgatacacgt ataaaaaata 84240 tagcataggc aatgactcct tatttttaga cattagatat gccaaaatca tagccccgct 84300 tctatttact cccgcagcac aatgaaccaa cacgggctcg tttcgttgat cacatttaga 84360 taaaaaggcg gttacgtcgt caaaatattt actaatatcg gtagttgtat catctaccaa 84420 cggtatatga ataatattaa tattagagtt aggtaatgta tatttatcca tcgtcaaatt 84480 taaaacatat ttgaacttaa cttcagatga tggtgcatcc atagcatttt tataatttcc 84540 caaatacaca ttattggtta cccttgtcat tatagtggga gatttggctc tgtgcatatc 84600 tccagttgaa cgtagtagta agtatttata caaacttttc ttatccattt ataacgtaca 84660 aatggataaa actactttat cggtaaacgc gtgtaattta gaatacgtta gagaaaaggc 84720 tatagtaggc gtacaagcag ccaaaacatc aacacttata ttctttgtta ttatattggc 84780 aattagtgcg ctattactct ggtttcagac gtctgataat ccagtcttta atgaattaac 84840 gagatatatg cgaattaaaa atacggttaa cgattggaaa tcattaacgg atagcaaaac 84900 aaaattagaa agtgatagag gtagacttct agccgctggt aaggatgata tattcgaatt 84960 caaatgtgtg gatttcggcg cctattttat agctatgcga ttggataaga aaacatatct 85020 gccgcaagct attaggcgag gtactggaga cgcgtggatg gttaaaaagg cggcaaaggt 85080 cgatccatct gctcaacaat tttgtcagta tttgataaaa cacaagtcta ataatgttat 85140 tacttgtggt aatgagatgt taaatgaatt aggttatagc ggttatttatta tgtcaccgca 85200 ttggtgttcc gattttagta atatggaata gtgttagata aatgcggtaa cgaatgttcc 85260 tgtaaggaac cataacagtt tagatttaac gttaaagatg agcataaaca taataaacaa 85320 aattacaatc aaacctataa cattaatatc aaacaatcca aaaaatgaaa tcagtggagt 85380 agtaaacgcg tacataactc ctggataacg tttagtagct gccgttccta ttctagacca 85440 aaaattcggt ttcatgtttt cgaaacggtg ttctgcaaca agtcggggat cgtgttctac 85500 atatttggcg gcattacca gtatctgcct attgatcttc atttcgtttt caattctggc 85560 tatttcaaaa taaaatcccg atgatagacc tccagacttt ataatttcat ctacgatgtt 85620 cagcgccgta gtaactctaa taatataggc tgataagcta acatcatacc ctcctgtata 85680 tgtgaatatg gcatgatttt tgtccattac aagctcggtt ttaactttat tgcctgtaat 85740 aatttctctc atctgtagga tatctatttt tttgtcatgc attgccttca agacgggacg 85800 aagaaacgta atatcctcaa taacgttatc gtttctaca ataactacat attctacctt 85860 tttatttct aactcggtaa aaaaattaga atcccatagg gctaaatgtc tagcgatatt 85920 tcttttcgtt tcctctgtac acatagtgtt acaaaaccct gaaaagaagt gagtatactt 85980 gtcatcattt ctaatgtttc ctccagtcca ctgtataaac gcataatcct tgtaatgatc 86040 tggatcatcc ttgactacca caacatttct tttttctggc ataacttcgt tgtcctttac 86100 atcatcgaac ttctgatcat taatatgctc atgaacatta ggaaatgttt ctgatggaag 86160 tctatcaata actggcacaa caataacagg agttttcgcc gccgccattt agttattgaa 86220 attaatcata tacaactctt taatacgagt tatattttcg tctatccatt gtttcacatt 86280 tacatatttc gacaaaaaga tataaaatgc gtattccaat gcttctctgt ttaatgaatt 86340 actaaaatat acaaacacgt cactgtctgg caataaatga tatcttagaa tattgtaaca 86400 atttattttg tattgcacat gttcgtgatc tatgagttct tcttcgaatg gcataggatc 86460 tccgaatctg aaaacgtata aataggagtt agaataataa tatttgagag tattggtaat 86520 atataaactc tttagcggta taattagttt ttttctctca atttctattt ttagatgtga 86580 tggaaaaatg actaattttg tagcattagt atcatgaact ctaatcaaaa tcttaatatc 86640 ttcgtcacac gttagctctt tgaagttttt aagagatgca tcagttggtt cgaccgatgg 86700 agtaggtgca acaatttttt gttcgatgta tgtatgtact ggagccattg ttttaactat 86760 aatggtgctt gtatcgaaaa actttaatgc agatagcgga agctcttcgc cgcgactttc 86820 tacatcgtaa ttgggttcta acgccgatct ctgaatggat actagttttc taagttctaa 86880 tgtgattctc tgaaaatgta aatccaattc ctccggcatt atagatgtgt atacatcggt 86940 aaataaaact atagtatcca acgatccctt ctcgcaaatt ctagtcttaa ccaaaaaatc 87000 gtatataacc acggagatgg cgtatttaag agtggattct tctaccgttt tgttcttgga 87060 tgtcatatag gaaactataa agtccgcact actgttaaga atgattacta acgcaactat 87120 atagttcaaa ttaagcattt tggaaacata aaataactct gtagacgata cttgactttc 87180 gaataagttt gcagacaaac gaagaaagaa cagacctctc ttaatttcag aagaaaactt 87240 tttttcgtat tcctgacgtc tagagtttat atcaataaga aagttaagaa ttagtcggtt 87300 aatgttgtat ttcattaccc aagtttgaga tttcataata ttatcaaaag acatgataat 87360 attaaagata aagcgctgac tatgaacgaa atagctatat ggttcgctca aaaatatagt 87420 cttgttaaac gtggaaacga taactgtatt tttaatcacg tcagcggcat ctaaattaaa 87480 tataggtata tttattccac acactctaca atatgccaca ccatcttcat aataaataaa 87540 ttcgttagca aaattattaa ttttagtgaa atagttagcg tcaactttca tagcttcctt 87600 caatctaatt tgatgctcac acggtgcgaa ttccactcta acatcccttt tccatgcctc 87660 aggttcatcg atctctataa tatctagttt tttgcgtttc acaaacacag gctcgtctct 87720 cgcgatgaga tctgtatagt aactatgtaa atgataacta gatagaaaga tgtagctata 87780 tagatgacga tcctttaaga gaggtataat aactttaccc caatcagata gactgttgtt 87840 atggtcttcg gaaaaagaat ttttataaat ttttccagta ttttccaaat atacgtactt 87900 aacatctaaa aaatccttaa tgataatagg aatggataat ccgtctattt tataaagaaa 87960 tacatatcgc acattatact tttttttgga aatgggaata ccgatgtgtc tacataaata 88020 tgcaaagtct aaatattttt tagagaatct taattggtcc aaattctttt ccaagtacgg 88080 taatagattt ttcatattga acggtatctt cttaatctct ggttctagtt ccgcattaaa 88140 tgatgaaact aagtcactat ttttataact aacgattaca tcacctctaa catcatcatt 88200 taccagaata ctgatcttct tttgtcgtaa atacatgtct aatgtgttaa aaaaaagatc 88260 atacaagtta tacgtcattt catctgtggt attcttgtca ttgaaggata aactcgtact 88320 aatctcttct ttaacagcct gttcaaattt atatcctata tacgaaaaaa tagcaaccag 88380 tgtttgatca tccgcgtcaa tattctgttc tatcgtagtg tataacaatc gtatatcttc 88440 ttctgtgata gtcgatacgt tataaaggtt gataacgaaa atatttttat ttcgtgaaat 88500 aaagtcatcg taggattttg gacttatatt cgcgtctagt agatatgctt ttatttttgg 88560 aatgatctca attagaatag tctctttaga gtccatttaa agttacaaac aactaggaaa 88620 ttggtttatg atgtataatt tttttagttt ttatagattc tttattctat acttaaaaaa 88680 tgaaaataaa tacaaaggtt cttgagggtt gtgttaaatt gaaagcgaga aataatcata 88740 aattatttca ttatcgcgat atccgttaag tttgtatcgt aatggcgtgg tcaattacga 88800 ataaagcgga tactagtagc ttcacaaaga tggctgaaat cagagctcat ctaaaaaata 88860 gcgctgaaaa taaagataaa aacgaggata ttttcccgga agatgtaata attccatcta 88920 ctaagcccaa aaccaaacga gccactactc ctcgtaaacc agcggctact aaaagatcaa 88980 ccaaaaagga ggaagtgggaa gaagaagtag ttatagagga atatcatcaa acaactgaaa 89040 aaaattctcc atctcctgga gtcagcgaca ttgtagaaag cgtggccgct gtagagctcg 89100 atgatagcga cggggatgat gaacctatgg tacaagttga agctggtaaa gtaaatcata 89160 gtgctagaag cgatctttct gacctaaagg tggctaccga caatatcgtt aaagatctta 89220 agaaaattat tactagaatc tctgcagtat cgacggttct agaggatgtt caagcagctg 89280 gtatctctag acaatttact tctatgacta aagctattac aacactatct gatctagtca 89340 ccgagggaaa atctaaagtt gttcgtaaaa aagttaaaac ttgtaagaag taaatgcgtg 89400 cactttttta taaagatggt aaactcttta ccgataataa ttttttaaat cctgtatcag 89460 acgataatcc agcgtatgag gttttgcaac atgttaaaat tcctactcat ttaacagatg 89520 tagtagtata tgaacaaacg tgggaggagg cgttaactag attaattttt gtgggaagcg 89580 attcaaaagg acgtagacaa tacttttacg gaaaaatgca tgtacagaat cgcaacgcta 89640 aaagagatcg tatttttgtt agagtatata acgttatgaa acgaattaat tgttttataa 89700 acaaaaatat aaagaaatcg tccacagatt ccaattatca gttggcggtt tttatgttaa 89760 tggaaactat gttttttat agatttggta aaatgaaata tcttaaggag aatgaaacag 89820 tagggttat aacactaaaa aataaacaca tagaaataag tcccgatgaa atagttatca 89880 agtttgtagg aaaggacaaa gtttcacatg aatttgttgt tcataagtct aatagactat 89940 ataaaccgct attgaaactg acggatgatt ctagtcccga agaatttctg ttcaacaaac 90000 taagtgaacg aaaggtatac gaatgtatca aacagtttgg tattagaatc aaggatctcc 90060 gaacgtatgg agtcaattat acgtttttat ataatttttg gacaaatgta aagtccatat 90120 ctcctcttcc atcaccaaaa aagttaatag cgttaactat caaacaaact gctgaagtgg 90180 taggtcatac tccatcaatt tcaaaaagag cttacatggc aacgactatt ttagaaatgg 90240 taaaggataa aaatttttta gatgtagtat ctaaaactac gttcgatgaa ttcctatcta 90300 tagtcgtaga tcacgttaaa tcatctacgg atggatgata tagatcttta cacaaataat 90360 tacaagaccg ataaatggaa atggataagc gtatgaaatc tctcgcaatg accgctttct 90420 ttggggagct aagcacatta gatattatgg cattgataat gtctatattt aaacgccatc 90480 caaacaatac cattttttca gtggataagg atggtcagtt tatgattgat ttcgaatacg 90540 ataattataa ggcttctcaa tatttggatc tgaccctcac tccgatattt ggagatgaat 90600 gcaagactca cgcatcgagt atagccgaac aattggcgtg tgcggatatt attaaagagg 90660 atattagcga atacatcaaa actactcccc gtcttaaacg atttataaaa aaataccgca 90720 atagatcaga tactcgcatc agtcgagata cagaaaagct taaaatagct ctagctaaag 90780 gcatagatta cgaatatata aaagacgctt gttaataagt aaatgaaaaa aaactagtcg 90840 tttataataa aacacaatat ggatgccaac atagtatcat cttctactat tgcaacgtat 90900 atagacgctt tagcgaagaa tgcttcagaa ttagaacaga ggtctaccgc atacgaaata 90960 aataatgaat tggaactagt atttattaag ccgccattaa ttactttgac aaatgtagtg 91020 aatatctcta cgattcagga atcgtttatt cgatttaccg ttactaataa ggaaggtgtt 91080 aaaattagaa ctaagattcc attatctaag gtacatggtc tagatgtaaa aaatgtacag 91140 ttagtagatg ctatagataa catagtttgg gaaaagaaat cattagtgac ggaaaatcgt 91200 cttcacaaag aatgcttgtt gagactatcg acagaggaac gtcatatatt tttggattac 91260 aagaaatatg gatcctctat ccgactagaa ttagtcaatc ttattcaagc aaaaacaaaa 91320 aactttacga tagactttaa gctaaaatat tttctaggat ccggtgccca atctaaaagt 91380 tctttgttgc acgctattaa tcatccaaag tcaaggccta atacatctct ggaaatagaa 91440 ttcacaccta gagacaatga aaaagttcca tatgatgaac taataaagga attgacgact 91500 ctatcacgtc atatattat ggcttctcca gagaatgtaa ttctttctcc gcctattaac 91560 gcacctataa agacttttat gttgcctaaa caagatatag taggtctgga tctggaaaat 91620 ctatatgccg taactaagac tgacggcatt cctataacta tcagagttac atcaaacggg 91680 ttgtattgtt attttacaca tcttggttat attattagat atcctgttaa gagaataata 91740 gattccgaag tagtagtctt tggtgaggca gttaaggata agaactggac cgtatatctc 91800 attaagctaa tagagcctgt gaatgcaatc aatgatagac tagaagaaag taagtatgtt 91860 gaatctaaac tagtggatat ttgtgatcgg atagtattca agtcaaagaa atatgaaggt 91920 ccgtttacta caactagtga agtcgtcgat atgttatcta catatttacc aaagcaacca 91980 gaaggtgtta ttctgttcta ttcaaaggga cctaaatcta acattgattt taaaattaaa 92040 aaggaaaata ctatagacca aactgcaaat gtagtattta ggtacatgtc cagtgaacca 92100 attatctttg gagaatcgtc tatctttgta gagtataaga aatttagcaa cgataaaggc 92160 tttcctaaag aatatggttc tggtaagatt gtgttatata acggcgttaa ttatctaaat 92220 aatatctatt gtttggaata tattaataca cataatgaag tgggtattaa gtccgtggtt 92280 gtacctatta agtttatagc agaattctta gttaatggag aaatacttaa acctagaatt 92340 gataaaacca tgaaatatat taactcagaa gattattatg gaaatcaaca taatatcata 92400 gttgaacatt taagagatca aagcatcaaa ataggagata tctttaacga ggataaacta 92460 tcggatgtgg gacatcaata cgccaataat gataaattta gattaaatcc agaagttagt 92520 tattttacga ataaacgaac tagaggaccg ttgggaattt tatcaaacta cgtcaagact 92580 cttcttattt ctatgtattg ttccaaaaca tttttagacg attccaacaa acgaaaggta 92640 ttggcgattg attttggaaa cggtgctgac ctggaaaaat acttttatgg agagattgcg 92700 ttattggtag cgacggatcc ggatgctgat gctatagcta gaggaaatga aagatacaac 92760 aaattaaact ctggaattaa aaccaagtac tacaaatttg actacattca ggaaactatt 92820 cgatccgata catttgtctc tagtgtcaga gaagtattct attttggaaa gtttaatatc 92880 atcgactggc agtttgctat ccattattct tttcatccga gacattatgc taccgtcatg 92940 aataacttat ccgaactaac tgcttctgga ggcaaggtat taatcactac catggacgga 93000 gacaaattat caaaattaac agataaaaag acttttataa ttcataagaa tttacctagt 93060 agcgaaaact atatgtctgt agaaaaaata gctgatgata gaatagtggt atataatcca 93120 tcaacaatgt ctactccaat gactgaatac attatcaaaa agaacgatat agtcagagtg 93180 tttaacgaat acggatttgt tcttgtagat aacgttgatt tcgctacaat tatagaacga 93240 agtaaaaagt ttattaatgg cgcatctaca atggaagata gaccgtctac aaaaaacttt 93300 ttcgaactaa atagaggagc cattaaatgt gaaggtttag atgtcgaaga cttacttagt 93360 tactatgttg tttatgtctt ttctaagcgg taaataataa tatggtatgg gttctgatat 93420 ccccgttcta aatgcattaa ataattccaa tagagcgatt tttgttccta taggaccttc 93480 caactgtgga tactctgtat tgttaataga tatattaata cttttgtcgg gtaacagagg 93540 ttctacgtct tctaaaaata aaagtttgat aacatctggc ctgttcataa ataaaaactt 93600 ggcgattcta tatatactct tattatcaaa tctagccatt gtctttataga tgtgagctac 93660 tgtaggtgta ccatttgatt ttctttctaa tactatatat ttctctcgaa gaagttcttg 93720 cacatcatct gggaataaaa tactactgtt gagtaaatca gttatttttt ttatatcgat 93780 attgatggac atttttatag ttaaggataa taagtatccc aaagtagata acgacgataa 93840 cgaagtattt atacttttag gaaatcacaa tgactttatc agatcaaaat taacaaaatt 93900 aaaggagcat gtattttttt ctgaatatat tgtgactcca gataaatatg gatctttatg 93960 cgtcgaatta aatgggtcta gttttcagca cggcggtaga tatatagagg tggaggaatt 94020 tatagatgct ggaagacaag ttagatggtg ttctacatcc aatcatatat ctgaagatat 94080 acccgaagat atacacactg ataaatttgt catttatgat atatacactt ttgacgcttt 94140 caagaataaa cgattggtat tcgtacaggt acctccgtcg ttaggagatg atagctattt 94200 gactaatccg ttattgtctc cgtattatcg taattcagta gccagacaaa tggtcaatga 94260 tatgattttt aatcaagatt catttttaaa atattttatta gaacatctga ttagaagcca 94320 ctatagagtt tctaaacata taacaatagt tagatacaag gataccgaag aattaaatct 94380 aacgagaata tgttataata gagataagtt taaggcgttt gtattcgctt ggtttaacgg 94440 cgtttcggaa aatgaaaagg tactagatac gtataaaaag gtatctaatt tgatataatg 94500 aattcagtga ctgtatcaca cgcgccatat actattactt atcacgatga ttgggaacca 94560 gtaatgagtc aattggtaga gttttataac gaagtagcca gttggctgct acgagacgag 94620 acgtcgccta ttcctgataa gttctttata cagttgaaac aaccgcttag aaataaacga 94680 gtatgtgtgt gcggtataga tccgtatccg aaagatggaa ctggtgtacc gttcgaatca 94740 ccaaatttta caaaaaaatc aattaaggag atagcttcat ctatatctag attaaccgga 94800 gtaattgatt ataaaggtta taaccttaat ataatagacg gggttatacc ctggaattat 94860 tacttaagtt gtaaattagg agaaacaaaa agtcacgcga tctactggga taagatttcc 94920 aagttactgc tgcagcatat aactaaacac gttagtgttc tttatgttt gggtaaaaca 94980 gatttctcga atatacgggc caagttagaa tccccggtaa ctaccatagt cggatatcat 95040 ccagcggcta gagaccgcca attcgagaaa gatagatcat ttgaaattat caacgtttta 95100 ctggaattag acaacaaggc acctataaat tgggctcaag ggtttattta ttaatgcttt 95160 agtgaaattt taacttgtgt tctaaatgga tgcggctatt agaggtaatg atgttatctt 95220 tgttcttaag actataggtg tcccgtcagc gtgcagacaa aatgaagatc caagatttgt 95280 agaagcattt aaatgcgacg agttagaaag atatattgag aataatccag aatgtacact 95340 attcgaaagt cttagggatg aggaagcata ctctatagtc agaattttca tggatgtaga 95400 tttagacgcg tgtctagacg aaatagatta tttaacggct attcaagatt ttattatcga 95460 ggtgtcaaac tggttagcta gattcgcgtt tacagaatgc ggcgccattc atgaaaatgt 95520 aataaaatcc atgagatcta atttttcatt gactaagtct acaaatagag ataaaacaag 95580 ttttcatatt atctttttag acacgtatac cactatggat acattgatag ctatgaaacg 95640 aacactatta gaattaagta gatcatctga aaatccacta acaagatcga tagacactgc 95700 cgtatatagg agaaaaacaa ctcttcgggt tgtaggtact aggaaaaatc caaattgcga 95760 cactattcat gtaatgcaac caccgcatga taatatagaa gattacctat tcacttacgt 95820 ggatatgaac aacaatagtt attacttttc tctacaacaa cgattggagg atttagttcc 95880 tgataagtta tgggaaccag ggtttatttc attcgaagac gctataaaaa gagtttcaaa 95940 aatattcatt aattctataa taaactttaa tgatctcgat gaaaataatt ttacaacggt 96000 accactggtc atagatacg taacaccttg tgcattatgt aaaaaacgat cgcataaaca 96060 tccgcatcaa ctatcgttgg aaaatggtgc tattagaatt tacaaaactg gtaatccaca 96120 tagttgtaaa gttaaaattg ttccgttaga tggtaataaa ctgtttaata ttgcacaaag 96180 aattttagac actaactctg ttttattaac cgaacgagga gaccatatag tttggattaa 96240 taattcatgg aaatttaaca gcgaagaacc cttgataaca aaactaattt tgtcaataag 96300 acatcaacta cctaaggaat attcaagcga attactctgt ccaagaaaac gaaagactgt 96360 agaagctaac atacgagaca tgttagtaga ttcagtagag accgatacct atccggataa 96420 acttccgttt aaaaatggtg tattggacct ggtagacgga atgttttaact ctggagatga 96480 tgctaaaaaa tatacgtgta ctgtatcaac cggatttaaa tttgacgata caaagttcgt 96540 cgaagacagt ccagaaatgg aagagttaat gaatatcatt aacgatatcc aaccattaac 96600 ggatgaaaat aagaaaaata gagagctata tgaaaaaaca ttatctagtt gtttatgtgg 96660 tgctaccaaa ggatgtttaa cattcttttt tggagaaact gcaactggaa agtcgacaac 96720 caaacgtttg ttaaagtctg ctatcggtga cctgtttgtt gagacgggtc aaacaatttt 96780 aacagatgta ttggataaag gacctaatcc atttatcgct aacatgcatt tgaaaagatc 96840 tgtattctgt agcgaactac ctgattttgc ctgtagtgga tcaaagaaaa ttagatctga 96900 caatattaaa aagttgacag aaccttgtgt cattggaaga ccgtgtttct ccaataaaat 96960 taataataga aaccatgcga caatcattat cgatactaat tacaaacctg tttttgatag 97020 gatagataac gcattaatga gaagaattgc cgtcgtgcga ttcagaacac acttttctca 97080 accttctggt agagaggctg ctgaaaataa tgacgcgtac gataaagtca aactattaga 97140 cgaggggtta gatggtaaaa tacaaaataa tagatataga ttcgcatttc tatacttgtt 97200 ggtgaaatgg tacagaaaat atcatgttcc tattatgaaa ctatatccta caccggaaga 97260 gattccggac tttgcattct atctcaaaat aggtactctg ttagtatcta gctctgtaaa 97320 gcatattcca ttaatgacgg acctctccaa aaagggatat atattgtacg ataatgtggt 97380 cactcttccg ttgactactt tccaacagaa aatatccaag tattttaatt ctagactatt 97440 tggacacgat atagagagct tcatcaatag acataagaaa tttgccaatg ttagtgatga 97500 atatctgcaa tatatattca tagaggatat ttcatctccg taaatatatg ctcatatatt 97560 tatagaagat atcacatatc taaatgaata ccggaatcat agatttattt gataatcatg 97620 ttgatagtat accaactata ttacctcatc agttagctac tctagattat ctagttagaa 97680 ctatcataga tgagaacaga agcgtgttat tgttccatat tatgggatca ggtaaaacaa 97740 taatcgcttt gttgttcgcc ttggtagctt ccagatttaa aaaggtttac attctagtgc 97800 ctaatatcaa cattttgaaa atttttaatt ataatatggg tgtagctatg aacttgttta 97860 atgacgaatt catagctgag aatatcttta ttcattccac aacaagtttt tattctctta 97920 attataacga taacgtcatt aattataacg gattatctcg ctacaataac tctattttta 97980 tcgttgatga ggcacataat atctttggga ataatactgg agaacttatg accgtgataa 98040 aaaataaaaa caagattcct tttctactat tgtctggatc tcccattact aacacaccta 98100 atactctggg tcatattata gatttaatgt ccgaagagac gatagatttt ggtgagatta 98160 ttagtcgtgg taagaaagta attcagacac ttcttaacga acgcggtgtg aatgtactta 98220 aggatttgct taaaggaaga atatcatatt acgaaatgcc tgataaagat ctaccaacga 98280 taagatatca cggacgtaag tttctagata ctagagtagt atattgtcac atgtctaaac 98340 ttcaagagag agattatatg attactagac gacagctatg ttatcatgaa atgtttgata 98400 aaaatatgta taacgtgtca atggcagtat tgggacaact taatctgatg aataatttag 98460 atactttatt tcaggaacag gataaggaat tgtacccaaa tctgaaaata aataatggcg 98520 tgttatacgg agaagaattg gtaacgttaa acattagttc caaatttaaa tactttatta 98580 atcggataca gacactcaac ggaaaacatt ttatatactt ttctaattct acatatggtg 98640 gattggtaat taaatatatc atgctcagta atggatattc tgaatataat ggttctcagg 98700 gaactaatcc acatatgata aacggcaaac caaaaacatt tgctatcgtt actagtaaaa 98760 tgaaatcgtc tttagaggat ctattagatg tgtataattc tcctgaaaac gatgatggca 98820 gtcaattgat gtttttgttt tcatcaaaca ttatgtccga atcctatact ctaaaagagg 98880 taaggcatat ttggtttatg actatcccag atactttttc tcaatacaac caaattcttg 98940 gacgatctat tagaaaattc tcttacgccg atatttctga accagttaat gtatatcttt 99000 tagccgccgt atattccgat ttcaatgacg aagtaacgtc attaaacgat tacacacagg 99060 atgaattgat taatgtttta ccatttgaca tcaaaaagct gttgtatcta aaatttaaga 99120 cgaaagaaac gaatagaata tactctattc ttcaagagat gtctgaaacg tattctcttc 99180 caccacatcc atcaattgta aaagttttat tgggagaatt ggtcagacaa tttttttata 99240 ataattctcg tattaagtat aacgactcca agttacttaa aatggttaca tcagttataa 99300 aaaataaaga agacgctagg aattacatag atgatattgt aaacggtcac ttctttgtat 99360 cgaataaagt atttgataaa tctcttttat acaaatacga aaacgatatt attacagtac 99420 cgtttagact ttcctacgaa ccatttgttt ggggagttaa ctttcgtaaa gaatataacg 99480 tggtatcttc tccataaaac tgatgaaata tataaagaaa taaatgtcga gctttgttac 99540 caatggatac cttccagtta cattggaacc acacgagctg acgttagaca taaaaactaa 99600 tattaggaat gccgtatata agacgtatct ccatagagaa attagtggta aaatggccaa 99660 gaaaatagaa attcgtgaag acgtggaatt acctctcggc gaaatagtta ataattctgt 99720 agttataaac gttccgtgtg taataaccta cgcgtattat cacgttgggg atatagtcag 99780 aggaacatta aacatcgaag atgaatcaaa tgtaactatt caatgtggag atttaatctg 99840 taaactaagt agagattcgg gtactgtatc atttagcgat tcaaagtact gcttttttcg 99900 aaatggtaat gcgtatgaca atggcagcga agtcactgcc gttctaatgg aggctcaaca 99960 aggtatcgaa tctagttttg tttttctcgc gaatatcgtc gactcataaa aaagagaata 100020 gcggtaagta taaacacgaa tactatggca ataattgcga atgttttatt ctcttcgata 100080 tatttttgat aatatgaaaa acatgtctct ctcaaatcgg acaaccatct cataaaatag 100140 ttctcgcgcg ctggagaggt agttgctgct cgtataatct ccccagaata atatacttgc 100200 gtgtcgtcgt tcaatttata cggatttcta tagttctctg ttatataatg cggttttcca 100260 tcatgattag acgacgacaa tagtgttctg aatttagata gttgatcaga atgaatgttt 100320 attggcgttg gaaaaattat ccatacagcg tctgcagagt ggttgatagt tgttcctaga 100380 tatgtaaaat aatccaactt actaggcagc aaattgtcta gataaaatac tgaatcaaac 100440 ggtgcagacg tattggcgga tctaatggaa tccaattgat taactatctt ttgaaaatat 100500 acatttttat gatccaatac ttgtaagaat atagaaataa tgataagtcc atcatcgtgt 100560 ttttttgcct cttcataaga actatatttt ttttattcc aatgaacaag attaatctct 100620 ccagagtatt tgtacacatc tatcaagtga ttggatccat aatcgtcttc ctttccccaa 100680 tatatatgta gtgatgataa cacatattca ttggggagaa accctccact tatatatcct 100740 cctttaaaat taatccttac tagttttcca gtgttctgga tagtggttgg tttcgactca 100800 ttataatgta tgtctaacgg cttcaatcgc gcgttagaaa ttgctttttt agtttctata 100860 ttaataggag atagttgttg cggcatagta aaaatgaaat gataactgtt taaaaatagc 100920 tcttagtatg ggaattacaa tggatgagga agtgatattt gaaactccta gagaattaat 100980 atctattaaa cgaataaaag atattccaag atcaaaagac acgcatgtgt ttgctgcgtg 101040 tataacaagt gacggatatc cgttaatagg agctagaaga acttcattcg cgttccaggc 101100 gatattatct caacaaaatt cagattctat ctttagagta tccactaaac tattacggtt 101160 tatgtactac aatgaactaa gagaaatctt tagacggttg agaaaaggtt ctatcaacaa 101220 tatcgatcct cactttgaag agttaatatt attgggtggt aaactagata aaaaggaatc 101280 tattaaagat tgtttaagaa gagaattaaa agaggaaagt gatgaacgta taacagtaaa 101340 agaatttgga aatgtaattc taaaacttac aacacgggat aaattattta ataaagtata 101400 tataagttat tgcatggcgt gttttattaa tcaatcgttg gaggatttat cgcatactag 101460 tatttacaat gtagaaatta gaaagattaa atcattaaat gattgtatta acgacgataa 101520 atacgaatat ctgtcttata tttataatat gctagttaat agtaaatgaa cttttacaga 101580 tctagtataa ttagtcagat tattaagtat aatagacgac tagctaagtc tattatttgc 101640 gaggatgact ctcaaattat tacactcacg gcattcgtta accaatgcct atggtgtcat 101700 aaacgagtat ccgtgtccgc tattttatta actactgata acaaaatatt agtatgtaac 101760 agacgagata gttttctcta ttctgaaata attagaacta gaaacatgtc tagaaagaaa 101820 cgattatttc tgaattattc caattatttg tccaaacagg aaagaagtat actatcgtca 101880 tttttttctc tagatccagc tactactgat aatgatagaa tagatgctat ttatccgggt 101940 ggcataccca aaaggggtga gaatgttcca gagtgtttat ccagggaaat taaagaagaa 102000 gttaatatag acaattcttt tgtattcata gacactcggt ttttattca tggcatcata 102060 gaagatacca ttattaataa attttttgag gtaatcttct ttgtcggaag aatatcttta 102120 acgagtgatc aaatcattga tacatttaaa agtaatcatg aaatcaagga tctaatattt 102180 ttagatccga attcaggtaa tggactccaa tacgaaattg caaaatatgc tctagatact 102240 gcaaaactca aatgttatgg ccatagagga tgttattacg aatcattaaa aaaattaact 102300 gaggatgatt gattagaaaa tataaattaa tttaccatcg tgtattttta taacgggatt 102360 gtccggcata tcatgtagat agttaccgtc tacatcgtat actcgaccat ctacgccttt 102420 aaatcctcta tttatgaca ttaatctatt agaattggaa taccaaatat tagtaccctc 102480 aattagttta ttggtaatat tttttttaga cgatagatcg atggctcttg aaaccaaggt 102540 tttccaaccg gactcattgt cgatcggtga gaagtctttt tcattagcat gaatccattc 102600 taatgatgta tgtttaaaca ctctaaacaa ttggacaaat tcttttgatt tgctttgaat 102660 gatttcaaat aggtcttcgt ctacagtagg cataccatta gataatctag ccattataaa 102720 gtgcacgttt acatatctac gttctggagg agtaagaacg tgactattga gacgaatggc 102780 tcttcctact atctgacgaa gagacgcctc gttccatgtc atatctaaaa tgaagatatc 102840 attaattgag aaaaaactaa taccctcgcc tccactagaa gagaatacgc atgttttaat 102900 gcattctccg ttagtgtttg attcttggtt aaactcagcc accgccttga ttctagtatc 102960 ttttgttcta gatgagaact ctatattaga gataccaaag actttgaaat atagtaataa 103020 gatttctatt cctgactgat taacaaatgg ttcaaagact agacatttac catgggatgc 103080 taatattccc aaacatacat ctataaattt gacgcttttc tcttttaatt cagtaaatag 103140 agagatatca gccgcactag catccccttt caatagttct ccctttttaa aggtatctaa 103200 tgcggattta gaaaactctc tatctcttaa tgaattttta aaatcattat atagtgttgc 103260 tatctcttgc gcgtattcgc ccggatcacg attttgtctt tcaggaaagc tatcgaacgt 103320 aaacgtagta gccatacgtc tcagaattct aaatgatgat atacctgttt ttatttcagc 103380 gagtttagcc ttttgataaa tttcttcttg ctttttcgac atattaacgt atcgcattaa 103440 tactgttttc ttagcgaatg atgcagaccc ttctacgtca tcaaaaatag aaaactcgtt 103500 attaactatg tacgaacata ggcctcctag tttggagact aattctttct catcaactag 103560 acgttattc tcaaatagcg attggtgttg taaggatcct ggtcgtagta agttaaccaa 103620 catggtgaat tcttgcacac tattaacgat aggtgtagcc gataaacaaa tcatcttatg 103680 gttttttaat gcgatggtct tagataaaaa attatatact gaacgagtag gacggatctt 103740 accatcttct ttgattaatg atttagaaat gaagttatga cattcatcaa taatgacgca 103800 tattctactc ttggaattaa tagttttgat attagtaaaa aatttatttc taaaattttg 103860 atcatcgtaa ttaataaaaa tacaatcctt cgttatctct ggagcgtatc tgagtatagt 103920 gttcatccaa ggatcttcta tcaaagcctt tttcaccaat aagataatag cccaattcgt 103980 ataaatatcc ttaagatgtt tgagaatata tacagtagtc attgttttac cgacacccgt 104040 ttcatggaac aataaaagag aatgcatact gtctaatcct aagaaaactc ttgctacaaa 104100 atgttgataa tccttgaggc gtactacgtc cgaccccatc atttcaacgg gcatattagt 104160 agttctgcgc aatgcataat cgatataggc cgcgtgtgat ttactcattt atgagtgata 104220 agtaataact atgttttaaa aatcacagca gtagtttaac tagtcttctc tgatgtttgt 104280 tttcgatact ttttgaatca gaagtcatac tagaataaag caacgagtga acgtaataga 104340 gagcttcgta tactctattc gaaaactcta agaacttatt aatgaattcc gtatccactg 104400 gattgtttaa aatactaaat tgaacactgt tcacatcctt ccaagaagaa gacttagtga 104460 cggacttaac atgagacata aataaatcca aatttttttt acaaacatca ctagccacca 104520 taatggcgct atctttcaac cagctatcgc ttacgcattt tagcagtcta acatttttaa 104580 agagactaca atatattctc atagtatcga ttacacctct accgaataaa gttggaagtt 104640 taataataca atatttttcg tttacaaaat caaataatgg tcgaaacacg tcgaaggtta 104700 acatcttata atcgctaatg tatagattgt tttcagtgag atgattatta gatttaatag 104760 catctcgttc acgtttgaac agtttattgc gtgcgctgag gtcggcaact acggcgtccg 104820 ctttagtact cctcccataa tactttacgc tattaatctt taaaatttca tagactttat 104880 ctagatcgct ttctggtaac atgatatcat gtgtaaaaag ttttaacatg tcggtcggca 104940 ttctatttag atcattaact ctagaaatct gaagaaagta attagctccg tattccagac 105000 taggtaatgg gcttttacct agagacagat taagttctgg caatgtttca taaaatggaa 105060 gaaggacatg cgttccctcc cggatatttt ttacaatttc atccatttac aactctatag 105120 tttgttttca ttattattag ttattatctc ccataatctt ggtaatactt accccttgat 105180 cgtaagatac cttatacagg tcattacata caactaccaa ttgtttttgt acataataga 105240 ttggatggtt gacatccatg gtggaataaa ctactcgaac agatagttta tctttccccc 105300 tagatacatt agccgtaata gttgtcggcc taaagaatat ctttggtgta aagttaaaag 105360 ttagggttct tgttccatta ttgctttttg tcagtagttc attataaatt ctcgagatgg 105420 gtccgttctc tgaatataga acatcatttc caaatctaac ttctagtcta gaaataatat 105480 cggtcttatt cttaaaatct attcccttga tgaagggatc gttaatgaac aaatccttgg 105540 cctttgattc ggctgatcta ttatctccgt tatagacgtt acgttgacta gtccaaagac 105600 ttacaggaat agatgtatcg atgatgttga tactatgtga tatgtgagca aagattgttc 105660 tcttagtggc atcactatat gttccagtaa tggcggaaaa ctttttagaa atgttatata 105720 taaaagaatt ttttcgtgtt ccaaacatta gcagattagt atgaagataa acactcatat 105780 tatcaggaac attatcaatt tttacataca catcagcatc ttgaatagaa acgataccat 105840 cttctggaac ctcaacaatc tcggcagact ccggataacc agtcggtggg ccatcactaa 105900 caataactag atcatccaac aatctactca catatgcatc tatataatct ttttcatctt 105960 gtgagtaccc tggatacgaa ataaatttat tatccgtatt tccataataa ggtttagtat 106020 aaacagagag cgatgttgcc gcatgaactt cagttacagt cgccgttggt tggtttattt 106080 gacctattac tctcctaggt ttctctataa acgatggttt aatttgtaca ttcttaacca 106140 tatatccaat aaagctcaat tcaggaacat aaacaaattc tttgttgaac gtttcaaagt 106200 cgaacgaaga gtcacgaata acgatatcgg atactggatt gaaggttacc gttacggtaa 106260 tttttgaatc ggatagttta agactgctga atgtatcttc cacatcaaac ggaggttttaa 106320 tataaacgta tactgtagat ggttctttaa tagtgtcatt aggagttagg ccaatagaaa 106380 tatcattaag ttcactagaa tatccagagt gtttcaaagc aattgtatta ttgatacaat 106440 tattatataa ttcttcgccc tcaatttccc aaataacacc gttacacgaa gagatagata 106500 cgtgattaat acatttatat ccaacatatg gtacgtaacc gaatcttccc atacctttaa 106560 cttctggaag ttccaaactc agaaccaaat gattaagcgc agtaatatac tgatccctaa 106620 tttcgaagct agcgatagcc tgattgtctg gaccatcgtt tgtcataact ccggatagag 106680 aaatatattg cggcatatat aaagttggaa tttgactatc gactgcgaag acattagacc 106740 gtttaataga gtcatcccca ccgatcaaag aattaatgat agtattattc attttctatt 106800 taaaatgggaa aaagcttaca ataaactccg tagagaaata tctataattt gtgagttttc 106860 cttaaagtaa cagcttccgt aaacgccgtc tttatctctt agtaagttta ttgtatttat 106920 aaccttttcc ttatcttcat agaatactaa aggcaacaaa gaaatttttg gttcttctct 106980 aagagctacg tgagacttaa ccatagacgc caacgaatcc ctacatattt tagaacagaa 107040 atacccaact tcaccaccct tgaatgtctc aatactaata ggtttaaaaa ccaaatcttg 107100 attacaaaac caacacttat caattacact atttgtctta atagacacat ctgccataga 107160 tttataatac tttggtagta tacaagcgag tgcttcttct ttagcgggct taaagactgc 107220 tttaggtgct gaaataacca catctggaag gcttactcgc ttagccattt aattacggaa 107280 ctattttttt atacttctaa tgagcaagta gaaaacctct catctacaaa aacatatactcg 107340 tgtccataat cctctaccat agttacacgt tttttagatc tcatatgtgc taaaaagttt 107400 tcccatacta attggttaact attatttttc gtataatttt taacagtttg aggttttaga 107460 tttttagtta cagaagtgat atcgaatatt ttatccaaaa agaatgaata attaattgtc 107520 ttagaaggag tgttttcttg gcaaaagaat accaagtgct taaatatttc tactacttca 107580 ttaatctttt ctgtactcag attcagtttc tcatctttta cttgattgat tatttcaaag 107640 actaacttat aatccttttt atttattctc tcgttagcct taagaaaact agatacaaaa 107700 tttgcatcta catcatccgt ggatatttga tttttttcca tgatatccaa gagttccgag 107760 ataatttctc cagaacattg atgagacaat aatctccgca atacatttct caaatgaata 107820 agtttattag acacatggaa gtttgacttt ttttgtacct ttgtacattt ttgaaatacc 107880 gactcgcaaa aaatacaata ttcatatcct tgttcagata ctataccgtt gtgtctacaa 107940 ccgctacata atcgtagatt catgttaaca ctctacgtat ctcgtcgtcc aatattttat 108000 ataaaaacat tttattcta gacgttgcca gaaaatcctg taatattttt agttttttgg 108060 gctgtgaata aagtatcgcc ctaatattgt taccgtcttc cgccaatata gtagttaaat 108120 tatccgcaca tgcaaaagaa caccgcttag gcggattcag tacaatgtta tatttttcgt 108180 accaactcat ttaaatatca taatctaaaa tagttctgta atatgtctag cgctaatata 108240 ttgatcataa tcctgtgcat aaattaagat acaacaatgt ctcgaaatca tcgacatggc 108300 ttcttccata gttagaagat cgtcgtcaaa gttagcaacg tgattcatca acatttgctg 108360 ttttgaggca gcaaatactg aaccgtcgcc attcaaccat tcataaaaac catcgtctga 108420 atccattgat aatttcttgt actggttttt gagagctcgc atcaatctag catttctagc 108480 tcccggattg aaaacagaaa gaggatcgta catccagggt ccattttctg taaatagaat 108540 cgtataatgt cccttcaaga agatatcaga cgatccacaa tcaaagaatt ggtctccgag 108600 tttgtaacaa actgcggact ttaacctata catgataccg tttagcatga tttctggtga 108660 tacgtcaatc ggagtatcat ctattagaga tctaaagccg gtgtaacatt ctccaccaaa 108720 catattctta ttctgacgtc gttctacata aaacatcatt gctccattaa cgataacagg 108780 ggaatgaaca gcactaccca tcacattagt tcccaatgga tcaatgtgtg taactccaga 108840 acatcttcca tatcctatgt taggaggagc gaacaccact cttccactat tgccatcgaa 108900 tgccatagaa taaatatcct tggaattgat agaaatcgga ctgtcggatg ttgtgatcat 108960 cttcatagga ttaacaacta tgtatggtgc cgcctgaagt ttcatatcgt aactgatgcc 109020 gtttataggt ctagccacag aaaccaacgt aggtctaaat ccaactatag acaaaataga 109080 agccaatatc tgttcctcat ctgtcataac ttgagagcat ccagtatgaa taatcttcat 109140 tagatgggga tctaccgcat catcatcgtt acaataaaaa attcccattc taatgttcat 109200 aattgctttt ctaatcatgg tatgcatgtt tgctctctga atctctgtgg aaattagatc 109260 tgatacacct gtaatcacta tcggattatc ctccgtaaga cgattaacca acaacatata 109320 attataagac tttacttttc taaattcata aagttgctgg attaggctat aggtgtctcc 109380 atgtacatac gcgttctcga gcgcaggaag tttaataccg aatagtgcca tcagaatagg 109440 atgaatatag taattagttt ctggttttct ataaataaaa gacaaatctt gtgaactaga 109500 catatcggta aaatgcatgg attggaatcg tgtagtcgac agaagaatat gatgattaga 109560 tggagagtat attttatcta actctttgag ttggtcaccg attctaggac tagctcgaga 109620 atgaataagt actaaaggat gagtacattt cacagaaaca ctagcattgt tcaatgtgct 109680 ctttacatgg gtaaggagtt gaaatagctc gtttctattt gttctgacaa tatttagttt 109740 attcataatg ttaagcatat cctgaatagt aaagttagat gtgtcatact tgttagtagt 109800 tagatattta gcaattgcat tcccatcatt tctcaatctc gtactccaat catgtgtaga 109860 tgctacttcg tcgatggaaa ccatacaatc ctttttgata ggctgttgag attgattatt 109920 tcctgcacgt ttaggtttgg tacgttgatt tctagcccct gcagatataa agtcatcgtc 109980 tacaattttg gataatgaat tgcatacact acaagacaaa gatttatcag aagtgtgaat 110040 atgatcttca tctaccaaag aaagagtttg attagtataa ctagatttta gtcctgcgtt 110100 agatgttaaa aaaacatcgc tattgaccac ggcttccatt atttatattc gtagttttta 110160 ctcgaaagcg tgattttaat atccaatctt attacttttg gaatcgttca aaacctttga 110220 ctagttgtag aatttgatct attgccctac gcgtatactc ccttgcatca tatacgttcg 110280 tcaccagatc gtttgtttcg gcctgaagtt ggtgcatatc tttttcaaca ctcgacatga 110340 gatccttaag ggccatatcg tctagatttt gttgagatgc tgctcctgga tttggatttt 110400 gttgtgctgt tgtacatact gtaccaccag taggtgtagg agtacataca gtggccacaa 110460 taggaggttg aggaggtgta accgttggag tagtacaaga aatacttcca tccgattgtt 110520 gtgtacatgt agttgttggt aacgtctgag aaggttgggt agatggcggt gtcgtcgtct 110580 tttgatcttt attaaattta gagataatat cctgaacagc attgctcggc gtcaacgctg 110640 gaaggagtga actcgccggc gcatcagtat ctgcagacag ccaatcaaaa agattagaca 110700 tatcagatga tgtattagtt tgttgtcgtg gttttggtgt aggagcagta ctactaggta 110760 gaagaatagg agccgatgta ggtgtcggaa ccggaaccgg ctgtggagtt atatgaatag 110820 ttggttgtag cggttggata ggctgtctgc tggcggccat catattatct ctagctagtt 110880 gttctcgcaa ctgtctttga taatacgact cttgagactt tagtcctatt tcaatcgctt 110940 catccttttt cgtatccgga tccttttttt cagaataata gattgacgac tttggtgtag 111000 aggattctgc cagcccctgt gagaacttgt taaagaagtc catttaaggc tttaaaattg 111060 aattgcgatt ataagattaa atggcagaca cagacgatat tatcgactat gaatccgatg 111120 atctcactga atacgaggat gatgaagaag aggaagaaga tggagagtca ctagaaacta 111180 gtgatataga tcccaaatct tcttataaga ttgtagaatc agcatccact catatagaag 111240 atgcgcattc caatcttaaa catataggga atcatatatc tgctcttaaa cgacgctata 111300 ctagacgtat aagtctattt gaaatagcgg gtataatagc agaaagctat aacttgcttc 111360 aacgaggaag attacctcta gtttcagaat tttctgacga aacgatgaag caaaatatgc 111420 tacatgtaat tatacaagag atagaggagg gttcttgtcc tatagtcatc gaaaagaacg 111480 gagaattgtt gtcggtaaac gattttgaca aagatggtct aaaattccat ctagactata 111540 ttatcaaaat ttggaaactt caaaaacgat attagaattt atacgaatat cgttctctaa 111600 atgtcacaat caagtctcgc atgttcagca atttattgtc gtactttata tcgtgttcat 111660 taacgatatc ttgcaaaata gtaatgattc tatcttcctt cgatagatat tcttcagaga 111720 ttattgtctt atattctttc ttgttatccg atatgaattt gataagactt tgaacattat 111780 taatacccgt ctgtttaatt ttttctacag atattttagt tttggcagat tctatcgtat 111840 ctgtcaatag acatccaaca tcgacattcg acgtcaattg tctataaatc aacgtataaa 111900 ttttagaaat aacattagcg aattgttgtg cattgatgtc gttattctga aacagtatga 111960 ttttaggtag cattttctta acaaagagaa cgtatttatt gttactcagt tgaacagatg 112020 atatatccag attactaacg catctgattc cgtataccaa actttcagaa gaaatggtgt 112080 acaattgttt gtattcattc aatgtctcct tttcagaaat tagtttagag tcgaatactg 112140 caataatttt caagagatag ttttcatcag ataagatttt atttagtgta gatatgataa 112200 aactattgtt ttgttggaga acttgatacg ccgcgttctc tgtagtcgac gctctcaaat 112260 gggaaacgat ctccattatt tttttggaat cggatactat atcttcggta tcttgacgca 112320 gtctagtata catagagtta agagagatta gagtttgtac attaagcaac atgtctctaa 112380 atgtggctac aaacttttcc tttttcacat catctagttt attatacc gatttcacaa 112440 cggcaccaga tttaaggaac cagaatgaaa aactctgata actacaatat ttcatcatag 112500 ttacgatttt atcatcttct atagttggtg taatagcgca tacctttttc tccaagactg 112560 gaaccaacgt cataaaaatg tttaaatcaa aatccatatc aacatctgat gcgctaagac 112620 cagtctcgcg ttcaagatta tcttactaa tggtgacgaa ctcatcgtat agaactctaa 112680 gtttgtccat tatttattta cagatttagt tgtttaattt atttgtgctc ttccagagtt 112740 gggatagtat ttttctaacg tcggtattat attattagga tctacgttca tatgtatcat 112800 aatattaatc atccacgttt tgataaatct atctttagct tctgaaataa cgtatttaaa 112860 caaaggagaa aaatatttag ctacggcatc agacgcaata acattttttg taaatgtaac 112920 gtatttagac gacagatctt cgttaaaaag ttttccatct atgtagaatc catcggttgt 112980 taacaccatt cccgcgtcag attgaatagg agtttgaata gtttgttttg gaaatagatc 113040 cttcaataac ttatagttgg gtgggaaaaa atcgatttta tcactagact ctttcttttt 113100 tactatcatt acctcatgaa ctatttcttg aatgagtata tgtattttct ttcctatatc 113160 ggacgcgttc attggaaaat ataccatgtc gttaactata agaatatttt tatcctcgtt 113220 tacaaactga ataatatcag atgtagttcg taaacgaact atatcatcac cagcacaaca 113280 tctaactata tgatatccac tagtttcctt tagccgttta ttatcttgtt ccatattagc 113340 agtcattcca tcatttaaga aggcgtcaaa aataataggg agaaatgaca ttttggattc 113400 tgttacgact ttaccaaaat taaggatata cggacttact atctttttct caacgtcaat 113460 ttgatgaaca cacgatgaaa atgtgcttct atgagattga tcatgtagaa aacaacaagg 113520 gatacaatat ttccgcatat catgaaatat attaagaaat cccaccttat tatatttccc 113580 caaaggatcc atgcacgtaa acattatgcc gttatcatta ataaagactt ctttctcatc 113640 ggatctgtaa aagttgttac tgattttttt cattccagga tctagataat taataatgat 113700 gggttttcta ttcttattct ttgtattttg gcatatccta gaccagtaaa cagtttccac 113760 tttggtaaaa tcagcagact tttgaacgct attaaacatg gcattaatgg caataactaa 113820 aaatgtaaaa tatttttcta tgttaggaat atggtttttc actttaatag atatatggtt 113880 tttggccaaa atgatagata tttttttatc cgaggatagt aaaatattat tagtcgccgt 113940 ctctataaaa atgaagctag tctcgatatc caattttatt ctagaattga taggagtcgc 114000 caaatgtacc ttatacgtta tatctccctt gatgcgttcc atttgtgtat ctatatcgga 114060 cacaagatct gtaaatagtt ttacgttatt aatcatcacg gtatcgccgt cgctagataa 114120 cgctaatgta ccatccaagt cccaaatgga gagatttaac tgttcatcgt ttagaataaa 114180 atgattaccg gtcatattaa taaagtgttc atcgtatcta gataacaacg acttataatt 114240 aatgtccaag tcttgaactc gctgaatgat cttttttaac ccagttagtt ttagattggt 114300 acgaaatata ttgttaaact ttgattctat agtaatgtcc aaatctagtt gtggaaatac 114360 ttccatcaac attgtttcaa acttgataat attattatct acatcttcgt acgatccaaa 114420 ttccggaata gatgtatcgc acgctctggc cacccagata accaaaaagt cacacgctcc 114480 aggatataca ttgtataaaa agctatcgtt ttttagtagg gtttttttct gcgtgtatac 114540 gaagggatta aaaatagtat tatcaacgta actatattcc aaattattct tatgagaata 114600 gataataata tcgtccttaa tatctaacaa atttcctaaa tatcccttta attgagtcat 114660 tcgaagcgtc aatagaatat gtctcttaac tatttccggc tgttgtatat ttaaatgact 114720 tcgtaaaaaa taatatatgg gcgacttctc atctatgtaa tcatatggag tgagatatag 114780 ggctcgttct acctcctgcc ccttacccac ctgtaatacc aattgcggac ttactatata 114840 tcgcatattt atatcgtggg gtaaagtgaa aatctactac cgatgatgta agtcttacaa 114900 tgttcgaacc agtaccagat cttaatttgg aggcctccgt agaactaggg gaggtaaata 114960 tagatcaaac aacacctatg ataaaggaga atagcggttt tatatccccgc agtagacgtc 115020 tattcgccca tagatctaag gatgatgaga gaaaactagc actacgattc tttttacaaa 115080 gactttattt tttagatcat agagagattc attatttgtt cagatgcgtt gacgctgtaa 115140 aagacgtcac tattaccaaa aaaaataaca ttatcgtggc gccttatata gcacttttaa 115200 ctatcgcatc aaaaggatgc aaacttacag aaacaatgat tgaagcattc tttccagaac 115260 tatataatga acatagtaag aaatttaaat tcaactctca agtatccatc atccaagaaa 115320 aactcggata ccagtttgga aactatcacg tttatgattt tgaaccgtat tactctacag 115380 tagctctggc tattcgagat gaacattcat ctggcatttt taatatccgt caagagagtt 115440 atctggtaag ttcattatct gaaataacat atagatttta tctaattaat ctaaaatctg 115500 atcttgttca atggagtgct agtacgggcg ctgtaattaa tcaaatggta aatactgtat 115560 tgattacagt gtatgaaaag ttacaactgg tcatagaaaa tgattcacaa tttacatgtt 115620 cattggctgt ggaatcaaaa cttccaataa aattacttaa agatagaaat gaattattta 115680 caaaattcat taacgagtta aaaaagacca gttcattcaa gataagcaaa cgcgataagg 115740 atacgctact aaaatatttt acttaggact ggagttagaa tttatagacg actcatttcg 115800 tttatcatta ttactaccat cattattagt attcttcttg ttatcttgtt cagaaatata 115860 cagcaatgct atgcctaata ctaaatacat tatcatgctt gcaatggctc taacaacgac 115920 gaaccaaaat gaatttggtc gtagcttttg ttcacaaaaa tacataaaga aatgtctaca 115980 taaatctatg gcgccattgg ctacttgaaa tagcgccagt cctcctacag attttaatat 116040 agctgtataa catgacattt attcatcatc aaaagagaca gagtcaccat ctgtcatatt 116100 tagatttttt ttcatgtgtt caaagtatcc tctactcatt tcattataat agtttatcat 116160 acttagaatt ttaggacgga tcaatgagta agacttgact agatcgtcag tagtaatttg 116220 tgcatcgtct attctgcatc cgcttcgtcg aataatgtat agcatcgctt tgagattctc 116280 catagctatc aagtctttat acaatgacat ggaaatatct gtgaatactt tatacttctc 116340 caacatcgat gccttaacat catcgcctac tttagcattg aaaatacgtt ctattgtgta 116400 gatggatgta acaagatttt taaacaacaa tgccatctta cacgatgatt gcctcaagtc 116460 tccaatcgtt tgtttagaac gattagctac agagtccaat gcttggctga ctagcatatt 116520 attatcttta gaaattgtat tcttcaatga ggcgtttatc atatctgtga tttcgttagt 116580 catattacag tctgactggg ttgtaatgtt atccaacata tcacctatgg atacggtaca 116640 cgtaccagca tttgtaataa tcctatctaa gatgttgtat ggcattgcgc agaaaatatc 116700 ttctcctgta atatctccac tctcgataaa tctactcaga ttattcttaa atgccttatt 116760 ctctggagaa aagatatcag tgtccatcat ttcattaata gtatacgcag aaaagatacc 116820 acgagtatca attctatcca agatacttat cggttccgag tcacagataa tggtttcctc 116880 tccttcggga gatcctgcat agaaatatct aggacaatag tttctatact gtctgtaact 116940 ctgataatct ctaaagtcac taactgatac catgaaattg agaagatcaa acgctgaagt 117000 aattaatttt tctgcctcgt ttttactaca actagttttc atcaatgtag tgacgatgta 117060 ttgtttagtt acttttggtc taatactgat gatagagata ttatattgcttc ccataatgga 117120 tcttctagta gtcaccttaa agcccattga tgcgaatagc agatagataa agtcttggta 117180 tgactccttt ctaatatagt acggactacc tttgtcaccc aactttatac ccacataagc 117240 cataacaacc tctttaatag ccgtttcatg aggtttatca gccatgagcc tgagtagttg 117300 gaagaatctc atgaatcccg tctcagaaag tcctatatgc atgatagatt tatctttcct 117360 gggaaactct cgtatagtca tagatgaaat actcttcaaa gtttctgaaa taagattagt 117420 aacagtctta cctccgacta ctctgggtaa caaacaaact ctaataggtg ttttctctgc 117480 ggagataata tcagaaagga tagagcaata agtagtatta ttgtgattat aaagaccgaa 117540 tacataacag gtagaattta taaacatcat gtcctgaagg tttttagact tgtattcctc 117600 gtaatccata ccgtcccaaa acatggattt ggtaactttg atagccgtag atctttgttc 117660 cttcgccaac aggttaaaga aattaataaa gaatttgttg tttctattta tgtccacaaa 117720 ttgcacgttt ggaagcgcca cggttacatt cactgcagca ttttgaggat cgcgagtatg 117780 aagtacgatg ttattgttta ctggtatatc tggaaagaaa tctaccagtc taggaataag 117840 agattgatat cgcatagaaa tagtaaagtt tataatctca tcatcgaaga gcattttgtt 117900 accattgtaa taaatatcca ctctgtcata tgtataaatg aagtactgtt caaacatgat 117960 gagatgttta tatgttggca tagtagtgag atcgacgttt ggtaatggca atgtattaag 118020 attaactcca taatgtctag cagcatctgc gatgttataa gcgtcgtcaa agcggggtcg 118080 atcttgtatt gttatatatt gtctaacacc tataagatta tcaaaatctt gtctgcttaa 118140 tacaccgtta acaatttttg ccttgaattc tttattggt gcattaataa catccttata 118200 gaggatgtta aacaaataag tgttatcaaa gttaagatct ggatatttct tttctgctag 118260 aacatccatt gagtcggagc catctggttt aatataacca ccgataaatc tagctctgta 118320 ttctgtatcc gtcaatctaa tattaagaag gtgttgagtg aaaggtgggaa gatcgtaaaa 118380 gctgtgagta ttaatgatag gattagtttc cgaactaatg ttaattgggg tattaataat 118440 atctatattt ccagcgttaa gtgtaacatt aaacagtttt aattcacgtg aagtagtatc 118500 aattaaataa ttaatgccca atttggatat agcagcctga agctcatctt gtttagttac 118560 ggatcctaat gagttattaa gcaatatatc gaacggatga acgaaggttg ttttgagttt 118620 gtcgcatact ttgtaatcta gacatagatg cggaagaacg gtagaaacta tacgaaataa 118680 atattcagag tcctctaatt gatcaagagt aactattgac ttaataggca tcatttattt 118740 agtattaaat gacgaccgta ccagtgacgg atatacaaaa cgatttaatt acagagtttt 118800 cagaagataa ttatccatct aacaaaaatt atgaaataac tcttcgtcaa atgtctattc 118860 taactcacgt taacaacgtg gtagatagag aacataatgc cgccgtagtg tcatctccag 118920 aggaaatatc ctcacaactt aatgaagatc tatttccaga tgatgattca ccggccacta 118980 ttatcgaacg agtacaacct catactacta ttattgacga tactccacct cctacgtttc 119040 gtagagagtt attaatatcg gaacaacgtc aacaacgaga aaaaagattt aatattacag 119100 tatcgaaaaa tgctgaagca ataatggaat ctagatctat gataacttct atgccaacac 119160 aaacaccatc cttgggagta gtttatgata aagataaaag aattcagatg ttagaggatg 119220 aagtggttaa tcttagaaat caacgatcta atacaaaatc atctgataat ttagataatt 119280 ttaccaaaat actatttggt aagactccgt ataaatcaac agaagttaat aagcgtatag 119340 ccatcgttaa ttatgcaaat ttgaacgggt ctccccttatc agtcgaggac ttggatgttt 119400 gttcagagga tgaaatagat agaatctata aaacgattaa acaatatcac gaaagtagaa 119460 aacgaaaaat tatcgtcact aacgtgatta ttatgtgtcat aaatattatc gagcaagcat 119520 tgctaaaact cggatttgaa gaaatcaaag gactgagtac cgatatcact tcagaaatta 119580 tcgatgtgga gatcggagat gactgcgatg ctgtagcatc aaaactagga atcggtaaca 119640 gtccggttct taatattgta ttgtttatac tcaagatatt cgttaaacga attaaaatta 119700 tttaatttaa tacattccca tatccagaca acaatcgtct ggattaatct gttcctgtcg 119760 tctcataccg gacgacatat taatcttttt attagtgggc atctttttag atggtttctt 119820 tttcccagca ttaactgagt cgatacctag aagatcgtga ttgatctctc cgaccattcc 119880 acgaacttct aattggccgt ctctgacggt accataaact attttaccag cattagtaac 119940 agcttggaca atctgaccat ccatcgcatt gtacgatgta gtagtaactg ttgttctacg 120000 tttaggagca ccagaagtat ttttggagcc cttggaggct gatgtagaag aagacgagga 120060 ttttgatttt ggtttacatg taatacattt tgaactcttt gattttgtat cacatgcgcc 120120 ggcagtcaca tctgtttgag aattaagatt attgttgcct cctttgacgg ctgcatctcc 120180 accgatttgc gctagtagat ttttaagctg tggtgtaatc ttattaactg tttcgatata 120240 atcatcgtaa ctgcttctaa cggctaaatt ttttttatcc gccatttaga agctaaaaat 120300 attttattt atgcagaaga tttaactaga ttatacaatg aactaatatg atccttttcc 120360 agattattta caaacttggt attttttggt tctggaggag gcgaatttaa attcggactt 120420 ggattcagat tttgtaagtt cttgatctta ttatacatcg agtataggat ggcgacagta 120480 actgctacac aaataccgat caaaagaaga ataccaatca tttattgaca ataacttcac 120540 tattgatcaa gtatgcaata tatcatcttt tcactaaata agtagtaata atgattcaac 120600 aatgtcgaga tatatggacg ataataattt agttcatgga aatatcgcta tgattggtgt 120660 gaatgactcc gctaactctg tggggtgcgc agtgctttcc ccacatagaa taaattagca 120720 ttccgactgt gataataata ccaagtataa acgccataat actcaatact ttccatgtac 120780 gagtgggact ggtagactta ctaaagtcaa taaaggcgaa gatacacgaa agaatcaaaa 120840 gaatgattcc agcgattagc acgccggaaa aataatttcc aatcataagc atcatgtcca 120900 tttaactaat aaaaatttta aatcgccgaa tgaacaaagt ggaatataaa ccatataaaa 120960 acaatagttt gtactgcaaa aataatatct atttttgttt tcgaagatat ggtaaaatta 121020 aatagtagta cacagcatgt tataactaac agcagcaacg gctcgtaatt acttatcatt 121080 tactagacga aaaggtggtg ggatattttc ttgctcaaat aatacgaata tatcacccat 121140 ccattttatg cgatgtttat atactctaat ctttaataga tctatagacg acgggtttac 121200 caacaatata gattttatcg attcatctaa tttaaaccct tccttaaacg tgaatgatct 121260 attatctggc ataacgatga ctctacctga tgaatcggac aatgtactgg gccatgtaga 121320 ataaattatc aacgaattat cgtctacgaa catttatatc atttgtttta attttaggac 121380 gcgaataaat ggatataaaa tagaaaataa cagatattac aaccagtgtt atggccgcgc 121440 ccaaccaggt aggcagtttt attttatctt ttactacagg ttctcctgga tgtacgtcac 121500 caacggcgga cgtagttcta gtacaattag acgtaagttc cgcttgggaa ttttttaacg 121560 ctaaagagtt aacgttaatc gtgcacccaa cgtatttaca tctagttctt tgaacatctt 121620 gattataata taaccatttt ctatctctag attcgtcggt gcactcatgt aaccaacata 121680 ccctaggtcc taaatattta tctccggaat tagattttgg ataattcgcg caccaacaat 121740 ttctatttcc tttatgatcg ttacaaaaga cgtataatgc cgtatcccca aaagtaaaat 121800 aatcaggacg aataattcta ataaactcag aacaatatct cgcatccata tgtttggagc 121860 aaatatcgga ataagtagac atagccggtt tccgttttgc acgtaaccat tctaaacaat 121920 tggggtttcc aggatcgttt ctacaaaatc cagtcatgaa atcgtcacaa tgttctgtct 121980 tgtaattatt attaaatatt tttggacagt gtttggtatt tgtcttagaa caacattttg 122040 ctacgctatc actatcgccc aggagataat ccttttttat aaaatgacat cgttgcccgg 122100 atgctatata atcagtagcg tgttttaaat ccttaatata ttcaggagtt acctcgttct 122160 gataatagat taatgatcca ggacgaaatt tgaaagaact acatggttct ccatgaatta 122220 atacatattg tttagcaaat tcaggaacta taaaactact acaatgatct atcgacatac 122280 catctatcaa acaaaacttg ggtttaattt ctcccggaga tgtttcataa tagtacgtat 122340 aactttcttc tgcaaactta acagctctat tatattcagg ataattaaaa cctaattcca 122400 tatatttgtc tcgtatatct gctattcctg gtgctatttt gattctatta agagtaacag 122460 ctgcccccat tcttaataat cgtcagtatt taaactgtta aatgttggta tatcaacatc 122520 taccttatt cccgcagtat aaggtttgtt gcaggtatac tgttcaggaa tggttacatt 122580 tatacttctt ctatagtcct gtctttcgat gttcatcaca tatgcaaaga acagaataaa 122640 caaaataatg taagaaataa tattaaatat ctgtgaattc gtaaatacat tgattgccat 122700 aataattaca gcagctacaa tacacacaat agacattccc acagtgttgc cattacctcc 122760 acgatacatt tgagttacta agcaataggt aataactaag ctagtaagag gcaatagaaa 122820 agatgagata aatatcatca atatagagat tagaggaggg ctatatagag ccaagacgaa 122880 caaaatcaaa ccgagtaacg ttctaacatc attatttttg aagattccca aataatcatt 122940 cattcctcca taatcgtttt gcatcatacc tccatcttta ggcataaacg attgctgctg 123000 ttcctctgta aataaatctt tatcaagcac tccagcaccc gcagagaagt cgtcaagcat 123060 attgtaatat cttaaataac tcatttatat attaaaaaat gtcactatta aagatggagt 123120 ataatcttta tgccgaacta aaaaaaatga cttgtggtca acccctaagt ctttttaacg 123180 aagacgggga tttcgtagaa gttgaaccgg gatcatcctt taagtttctg atacctaagg 123240 gattttacgc ctctccttcc gtaaagacga gtctagtatt cgagacatta acaacgaccg 123300 ataataaaat cactagtatc aatccaacaa atgcgccaaa gttatatcct cttcaacgca 123360 aagtcgtatc tgaagtagtt tctaatatga ggaaaatgat cgaatcaaaa cgtcctctat 123420 acattactct tcacttggcg tgtggatttg gtaagactat taccacgtgt tatcttatgg 123480 ctacacacgg tagaaaaacc gtcatttgcg tacccaataa aatgttaata catcaatgga 123540 agacacaggt agaggcagtc ggattggaac ataagatatc catagatgga gtaagtagtc 123600 tattaaagga actaaagact caaagtccgg atgtattaat agtagtcagt agacatctga 123660 caaacgatgc cttttgtaaa tatatcaata agcattatga tttgttcatc ttggatgaat 123720 cacatacgta taatctgatg aacaatacag cagttacaag atttttagcg tattatcctc 123780 cgatgatgtg tattttttta actgctacac ctagaccatc taacagaatt tattgtaaca 123840 gtattattaa tattgccaag ttatccgatc taaaaaaac tatctatgcg gtagatagtt 123900 tttttgagcc atattccaca gacaatatta gacatatgat aaaacgatta gatggaccat 123960 ctaataaata tcatatatat actgagaagt tattatctgt agacgagcct agaaatcaac 124020 ttattcttga taccctggta gaagaattca agtcaggaac tattaatcgc attttagtta 124080 ttactaaact acgtgaacat atggtattct tctacaaacg attattagat cttttcggac 124140 cagaggttgt atttatagga gacgcccaaa atagacgtac tccagatatg gtcaaatcaa 124200 tcaaggaact aaatagattt atattcgtat ccaccttatt ttattccggt actggtttag 124260 atattcctag tttggattcg ttgttcattt gctcggcagt aatcaacaat atgcaaatag 124320 agcaattact agggagggta tgtcgagaaa cagaactatt agataggacg gtatatgtat 124380 ttcctaacac atccatcaaa gaaataaagt acatgatagg aaatttcatg caacgaatta 124440 ttagtctgtc tgtagataaa ctaggattta aacaaaaaag ttatcggaaa catcaagaat 124500 ccgatccac ttctgtatgt acaacatcct ccagagaaga acgtgtatta aatagaatat 124560 ttaactcgca aaatcgttaa gaagtttaag cgacgatccg catgctgcgc aggccagtgt 124620 attaccctc atagtattaa tataatccaa tgatactttt gtgatgtcgg aaatcttaac 124680 caatttagac tgacaggcag aacacgtcat gcaatcatca tcgtcatcga taactgtagt 124740 cttgggcttc tttttgcggc tcttcattcc ggaacgcaca ttggtgctat ccatttaggt 124800 agtaaaaaat aagtcagaat atgccctata gcacgatcgt gcaaaacctg gtatatcgtc 124860 tctatcttta tcacaatata gtgtatcgac atctttatta ttatgacct cgtttatctt 124920 ggaacatgga atgggaacat ttttgttatc aacggccatc tttgccttaa ttccagatgt 124980 tgtaaaatta taactaaaca gtctatcatc gacacaaatg aaattcttgt ttagacgttt 125040 gtagtttacg tatgcggctc gttcgcgtct cattttttca gatattgcag gtactataat 125100 attaaaaata agaatgaaat aacataggat taaaaataaa gttatcatga cttctagcgc 125160 tgatttaact aacttaaaag aattacttag tctgtacaaa agtttgagat tttcagattc 125220 tgcggctata gaaaagtata attctttggt agaatgggga acatctactt actggaaaat 125280 aggcgtgcaa aaggtagcta atgtcgagac gtcaatatct gattattatg atgaggtaaa 125340 aaataaaccg tttaatattg atccgggcta ttacattttc ttaccggtat attttgggag 125400 cgtctttatt tattcgaagg gtaaaaatat ggtagaactt ggatctggaa actcttttca 125460 aataccagat gatatgcgaa gtgcgtgtaa caaagtatta gacagcgata acggaataga 125520 ctttctgaga tttgttttgt taaacaatag atggataatg gaagatgcta tatcaaaata 125580 tcagtctcca gttaatatat ttaaactagc tagtgagtac ggattaaaca tacccaaata 125640 tttagaaatt gaaatagagg aagacacatt atttgacgac gagttatact ctattataga 125700 acgctctttc gatgataaat ttccaaaaat atccatatcg tatattaagt tgggagaact 125760 taggcggcaa gttgtagact ttttcaaatt ctcgttcatg tatattgagt ccatcaaggt 125820 agatcgtata ggagataata ttttattcc tagcgttata acaaaatcag gaaaaaagat 125880 attagtaaaa gatgtagacc atttaatacg atccaaggtt agagaacata catttgtaaa 125940 agtaaaaaag aaaaacacat tttccatttt atacgactat gatggaaacg gaacagaaac 126000 tagaggagaa gtaataaaac gaattataga cactatagga cgagactatt atgttaacgg 126060 aaagtatttc tctaaggttg gtagtgcagg cttaaagcaa ttgactaata aattagatat 126120 taatgagtgc gcaactgtcg atgagttagt tgatgagatt aataaatccg gaactgtaaa 126180 acgaaaaata aaaaaccaat cagcatttga tttaagcaga gaatgtttgg gatatccaga 126240 agcggatttt ataacgttag ttaataacat gcggttcaaa atagaaaatt gtaaggttgt 126300 aaatttcaat attgaaaata ctaattgttt aaataacccg agtattgaaa ctaattatgg 126360 aaactttaac cagttcgtct caatctttaa tatcgtcacc gatgtcaaaa aaagattatt 126420 cgagtgaaat aatatgcgcc tttgatatag gtgcaaaaaa tcctgccaga actgttttag 126480 aagtcaagga taactccgtt agggtattgg atatatcaaa attagactgg agttctgatt 126540 gggaaaggcg catagctaaa gatttgtcac aatatgaata cactacagtt cttctagaac 126600 gtcagcctag aaggtcgccg tatgttaaat ttatctattt tattaaaggc tttttatatc 126660 atacatcggc tgccaaagtt atttgcgtct cgcctgtcat gtctggtaat tcatatagag 126720 atcgaaaaaa gagatcggtc gaagcatttc ttgattggat ggacacattc ggattgcgag 126780 actccgttcc ggatagacgc aaattagacg atgtagcgga tagtttcaat ttggctatga 126840 gatacgtatt agataaatgg aatactaatt atacacctta taatagggtgt aaatctagaa 126900 attacataaa aaaaatgtaa taacgttagt aacgccatta tggataatct atttaccttt 126960 ctacatgaaa tagaagatag atatgccaga actattttta actttcatct aataagttgc 127020 gatgaaatag gagatatata tggtcttatg aaagaacgca tttcctcaga ggatatgttt 127080 gataatatag tgtataataa agatatacat cctgccatta agaaactagt gtattgcgac 127140 atccaactta ctaaacacat tattaatcag aatacgtatc cggtatttaa cgattcttca 127200 caagtgaaat gttgtcatta tttcgacata aactcagata atagcaatat tagctctcgt 127260 acagtagaga tatttgagag ggaaaagtca tctcttgtat catatattaa aactaccaat 127320 aagaagagaa aggtcaatta cggcgaaata aagaaaactg ttcatggagg cactaatgca 127380 aattactttt ccggtaaaaa gtctgacgag tatctgagta ctacagttag atccaacatt 127440 aatcaacctt ggatcaaaac catctctaag aggatgagag ttgatatcat taatcactct 127500 atagtaacgc gtggaaaaag ctctatatta caaactatag aaattatttt tactaataga 127560 acatgtgtga aaatattcaa ggattctact atgcacatta ttctatccaa ggacaaggat 127620 gaaaaggggt gtatacacat gattgacaaa ttattctatg tctattataa tttattctg 127680 ttgttcgagg atatcatcca aaacgagtac tttaaagaag tagctaatgt tgtaaaccac 127740 gtactcacgg ctacggcatt agatgagaaa ttattcctaa ttaagaaaat ggctgaacac 127800 gatgtttatg gagttagcaa tttcaaaata gggatgttta acctgacatt tattaagtcg 127860 ttggatcata ccgttttccc ctctctgtta gatgaggata gcaaaataaa gttttttaag 127920 gggaaaaagc tcaatattgt agcattacga tctctggagg attgtataaa ttacgtgact 127980 aaatccgaga atatgataga aatgatgaag gaaagatcga ctattttaaa tagcatagat 128040 atagaaacgg aatcggtaga tcgtctaaaa gaattgcttc taaaatgaaa aaaaacactg 128100 attcagaaat ggatcaacga ctcggatata agtttttggt gcctgatcct aaagccggag 128160 ttttttatag accgttacat ttccaatatg tatcgtattc taattttata ttgcatcgat 128220 tgcatgaaat cttgaccgtc aagcggccac tcttatcgtt taagaataat acagaacgaa 128280 ttatgataga aattagcaat gttaaagtga ctcctccaga ttatcacct ataatcgcga 128340 gtattaaagg taagagttat gacgcattag ccacgttcac tgtaaatatc tttaaagagg 128400 taatgaccaa agagggtata tccatcacta aaataagtag ttatgaggga aaagattctc 128460 atttgataaa aattccgcta ctaataggat acgggaataa aaatccactt gatacagcca 128520 agtatcttgt tcctaatgtc ataggtggag tctttatcaa taaacaatct gtcgaaaaag 128580 taggaattaa tctagtagaa aagattacaa catggccaaa atttagggtt gttaagccaa 128640 actcattcac tttctcgttt tcctccgtat cccctcctaa tgtattaccg acaagatatc 128700 gccattacaa gatatctctg gatatacac aattggaagc gttgaatata tcatcgacaa 128760 agacatttat aacggtcaat attgttttgc tgtctcaata tttatctaga gtgagtctag 128820 aattcattag acgtagttta tcatacgata tgcctccaga agttgtctat ctagtaaacg 128880 cgataataga tagtgctaaa cgaattactg aatctattac tgactttaat attgatacat 128940 acattaatga cctggtggaa gctgaacaca ttaaacaaaa atctcagtta acgattaacg 129000 agttcaaata tgaaatgctg cataactttt tacctcatat gaactataca cccgatcaac 129060 taaagggatt ttatatgata tcttactaa gaaagtttct ctactgtatc ttccacactt 129120 ctagatatcc agatagagat tcgatggttt gtcatcgcat cctaacgtac ggcaaatatt 129180 ttgagacgtt ggcacatgat gaattagaga attacatagg caacatccga aacgatatca 129240 tgaacaatca caagaacaga ggcacttacg cggtaaacat tcatgtacta acaactcccg 129300 gacttaatca cgcgttttct agcttattga gtggaaagtt caaaaagtca gacggtagtt 129360 atcgaacaca tcctcactat tcatggatgc agaatatttc tattcctagg agtgttggat 129420 tttatccgga tcaagtaaag atttcaaaga tgttttctgt cagaaaatac catccaagtc 129480 aatatcttta cttttgttca tcagacgttc cggaaagagg tcctcaggta ggtttagtat 129540 ctcaattgtc tgtcttgagt tccattacaa atatactaac gtctgagtat ttggatttgg 129600 aaaagaaaat ttgtgagtat atcagatcat attataaaga tgatataagt tactttgaaa 129660 caggatttcc aatcactata gaaaatgctc tagtcgcatc tcttaatcca aatatgatat 129720 gtgattttgt aactgacttt agacgtagaa aacggatggg attcttcggt aacttggagg 129780 taggtattac tttagttagg gatcacatga atgaaattcg cattaatatt ggagcgggaa 129840 gattagtcag accattcttg gttgtggata acggagagct catgatggat gtgtgtccgg 129900 agttagaaag cagattagac gacatgacat tctctgacat tcagaaagag tttccgcatg 129960 tcatcgaaat ggtagatata gaacaattta cttttagtaa cgtatgtgaa tcggttcaaa 130020 aatttagaat gatgtcaaag gatgaaagaa agcaatacga tttatgtgac tttcctgccg 130080 aatttagaga tggatatgtg gcatcttcat tagtgggaat caatcacaat tctggaccca 130140 gagctattct tggatgtgct caagctaaac aagctatctc ttgtctgagt tcggatatac 130200 gaaataaaat agacaatgga attcatttga tgtatccaga gaggccaatc gtgattagta 130260 aggctttaga aacttcaaag attgcggcta attgcttcgg ccaacatgtt actatagcat 130320 taatgtcgta caaaggtatc aatcaagagg atggaattat catcaaaaaa caatttattc 130380 agagaggcgg tctcgatata gttaccgcaa agaaacatca agtagaaatt ccattggaaa 130440 actttaataa caaagaaaga gataggtcta acgcctattc aaaattagaa agtaatggat 130500 tagttagact gaatgctttc ttggaatccg gagacgctat ggcacgaaat atctcatcaa 130560 gaactcttga agatgatttt gctagagata atcagattag cttcgatgtt tccgagaaat 130620 ataccgatat gtacaaatct cgcgttgaac gagtacaagt agaacttact gacaaagtta 130680 aggtacgagt attaaccatg aaagaaagaa gacccattct aggagacaaa tttaccacta 130740 gaacgagtca aaagggaaca gtcgcgtatg tcgcggatga aacggaactt ccatacgacg 130800 aaaatggtat cacgccagat gtcattatta attctacatc catcttctct agaaaaacta 130860 tatctatgtt gatagaagtt attttaacag ccgcatattc tgctaagccg tacaacaata 130920 agggaaaaa ccgacctgtc tgttttccta gtagtaacga aacatccatc gatacatata 130980 tgcaattcgc taaacaatgt tatgagcatt caaatccgaa attgtctgat gaagaattat 131040 cggataaaat cttttgtgaa aagattctct atgatcctga aacggataag ccttatgcat 131100 ccaaagtatt ttttggacca atttatact tgcgtctgag acatttaact caggacaagg 131160 caaccgttag atgtagaggt aaaaagacga agctcattag acaggcgaat gagggacgaa 131220 aacgtggagg aggtatcaag ttcggagaaa tggagagaga ctgtttaata gcgcatggcg 131280 cagccaatac tattacagaa gttttgaaag attcggaaga agattatcaa gatgtgtatg 131340 tttgtgaaaa ttgtggagac atagcagcac aaatcaaggg tattaataca tgtcttagat 131400 gttcaaaact taatctctct cctctcttaa caaaaattga taccacgcac gtatctaaag 131460 tatttcttac tcaaatgaac gccagaggcg taaaagtcaa attagatttc gaacgaagac 131520 ctccttcgtt ttataaacca ttagataaag ttgatctcaa gccgtctttt ctggtgtaat 131580 attctagttt ggtagtagat acatatcaat atcatcaaat tcgagatccg aattataaaa 131640 tgggcgtgga ttgttaacta tagaatcgga cgtctgatat tcgaaaatct gtggagtttc 131700 aggttttggt ggaggtgtaa ctgctacttg ggatactgaa gtctgatatt cagaaagctg 131760 tggatgttct ggttcggcat ccaccgatgg tgtcacatca ctaatcggtt cggtaacgtc 131820 tgtggatgga ggtgctactt ctacagaacc tgtagcctca gttgtcaacg gagatact 131880 tttaatgcga gaaaatgtat aatttggtaa tggtttctca tgtggatctg aagaagaggt 131940 aagatatcta ctagaaagat accgatcacg ttctagttct cttttgtaga acttaacttt 132000 ttctttctcc gcatctagtt gatattccaa cctcttcacg ttactacgtt cagattccaa 132060 ttcacgttcg catgggttac ctccgcagtt tttacgagcg atttcacgtt cagccttcat 132120 gcgtctctcc ctctctctat cgagtttatc agagcagtct ttctgaaggc gatcgaactc 132180 cataaatttc tccaacgctt tgattgtttc catagatttc cgaacttcag cttctaggac 132240 ggcgattctt tttctttcga attcacagct ggatgtacaa ccgtttccat taccgccatc 132300 tctaagtttc ttttctagat cggcaacatt tcatccccat gccttttaca ttcctcgagt 132360 ctactgtcgt cgaaatatcg ttccagctcc ttttcgacat caataacttt agcacgttgt 132420 ctctcaagct ctcttttgta gttatctgat tccctggcac gtttaagatc ttcatgcaat 132480 tgagtcagct cttaacttcc tctcttgctt cttcgtcata gtacgcgcaa tcactgtgag 132540 atccattgtt accacgtcta cactcggcga gctcgcgttt aagagattca atttcccgtt 132600 tgtattggtc catgtttcca ttgctaccac cattagattt acaggctgct agttgtcgtt 132660 cgagatcaga aatacgggtt ttcttggaat tgatttcgtc gatgtacttg gcatcgaaac 132720 acttattaag ttctttttcc aattctacga ttttatttct ttcgcgagtc aattccctcc 132780 tgtagtaact atctgttttg tcagattcac gctctctacg tagactttct tgcaagttac 132840 taatttgttc cctagcacgt ccgagtttag ttttatatgc tgaatagagt tctgattcat 132900 cctttgagca gatctctagc gatcgtttaa gattcctgat tctagtcttt agcctattta 132960 cctcctcaga agatgttccg ttaccgttgc gtttacactc gttaagctgt ctatcaagat 133020 ccatgattct atctctaaga cgttgcatct ctctttccat atcagcattg ctttcattat 133080 tacgtctgca gtcactcaac tgtctttcaa tatctgagat tctatctcta agacgtcgca 133140 tctctctctg tttcagcatt ggtttcatta ttacgtctac agtcgttcaa ctgtctttca 133200 agatctgata ttctagattg gagtctgcta atctctgtag cattttcacg gcattcactc 133260 agttgtcttt caagatctga aattttagat tggagtctgc taatctctgt aagatttcct 133320 cctccgctct cgatgcagtt ggtcaactta ttctctagtt ctctaatacg cgaacgcagt 133380 gcatcaactt cttgcgtgtc ttcctggttg cgtgtacatt catcgagtct agattcgaga 133440 tctctaacgc gtcgtcgttc ttcctcaagt tctctgcgta ctacagaaag cgtgtcccta 133500 tcttgttgat atttagcaat ttctgattct agagtactga ttttgcttac gtagtacta 133560 atagttgtct tggccttatc aagatcctcc ttgtatttgt cgcattcctt gatatcccta 133620 cgaagtctgg acagttccca ttcgacatta cgacgtttat cgatttcagc tcggagatcg 133680 tcatcgcgtt gttttagcca catacgactg agttcaagtt ctcgttgaca agatccatct 133740 acttttccat tcctaatagt atccagttcc ttttctagtt ctgaacgcat ttctcgttcc 133800 ctatcaagcg attctctcaa ttctcggata gtcttcttat caatttctaa taaatctgaa 133860 ccatcatctg tcccattttg aatatccctg tgttctttga tctcttttgt aagtcggtcg 133920 attctttcgg ttttataaac agaatccctt tccaaagtcc taatcttact gagtttatca 133980 ctaagttctg cattcaattc ggtgagtttt ctcttggctt cttccaactc tgttttaaac 134040 tctccactat ttccgcattc ttcctcgcat ttatctaacc attcaattag tttattaata 134100 actagttggt aatcagcgat tcctatagcc gttcttgtaa ttgtgggaac ataattagga 134160 tcttctaatg gattgtatgg cttgatagca tcatctttat cattattagg gggatggaca 134220 accttaattg gttggtcctc atctcctcca gtagcgtgtg gttcttcaat accagtgtta 134280 gtaataggct taggcaaatg cttgtcgtac gcgggcactt cctcatccat caagtattta 134340 taatcgggtt ctacttcaga atattctttt ctaagagacg cgacttcggg agttagtaga 134400 agaactctgt ttctgtatct atcaacgctg gaatcaatac tcaagttaag gatagcgaat 134460 acctcatcgt catcatccgt atcttctgaa acaccatcat atgacatttc atgaagtcta 134520 acgtattgat aaatagaatc agatttagta ttaaacagat ccttaacctt tttagtaaac 134580 gcatatgtat attttagatc tccagatttc ataatatgat cacatgcctt aaatgtcagt 134640 gcttccatga tataatctgg aacactaatg ggtgacgaaa aagatacagc accatatgct 134700 acgttgataa ataaatctga accactaagt agataatgat taatgttaag gaaaagaaaa 134760 tattcagtgt ataggtatgt cttggcgtca tatcttgtac taaacacgct aaacagtttg 134820 ttaatgtgat caatttccaa tagattaatt agagcagcgg gaataccaac aaacatatta 134880 ccacatccgt attttctatg aatatcacat atcatgttaa aaaatcttaa tagaagagcg 134940 aatatctcgt ctgacttaat gagacgtagt tcagcagcaa cataagtcat aactgtaaat 135000 agaacatact ttcctgtagt gttgattcta gactccacat caacaccatt attaaaaata 135060 gttttatata catctttaat ctgctctccg ttaatcgtcg aacgttctag tatacggaaa 135120 cactttgatt tctttctgt agttaatgac ttagtgatat cacgaagaat attacgaatt 135180 acatttcttg tttttcttga gagacctgat tcagaactca actcatcgtt ccatagtttt 135240 tctacctcag tggcgaaatc tttggagtgc ttggtacatt tttcaataag gttcgtgacc 135300 tccatttatt ataaaaaatt tattcaaaac ttaactacaa tcgggtaatt ataagatcgt 135360 aaatctccca tgtggcggaa tactaccatc tatcgcatgt ggatggacag taggtaatgg 135420 ccatgggaac agtaatgatt gcatatttat ctttcttgct agtattactg catattgtcc 135480 caatgtttcg atgtgatgtt ctaacctatc aactgccgct gtatcacaac aatagtgtcc 135540 gatgaaatta agattatgat ccaatgtgtt taatatatga ttatcaagtc ttatacgatc 135600 cgcgtctttt ttgacaggat caggttcttc tacaggaaga agtttcggcc tcttatgata 135660 ttcatgtctg ggaaacggtg gtctagggtg aggctccggt atcggagtgg gttttggatt 135720 ataatcatca tcgtctatga catcatcatc atcttcgact tcgatattta ttttgctatc 135780 ttgatgatgt cctgtatcag ttgcattttc agcactcgac tgaatattag cgcattcatt 135840 gtctattatt accatatttc taaacccaaa atgtatgtgt tgaacatcag tactatcgtt 135900 gatgagtctt atagcatgaa ttcgcttatc gttatcgggt ttatcttctg tcaccttagc 135960 aattcctttt ttattaaact ctacataatc atatccattt ctattgtttg ttctaatata 136020 aacgagtata gcatcattgc taaatttttc aatagtatcg aaaacagaat atcctaaacc 136080 atataatata tattcaggga cactcaaact aaatgtccag gattctccta aatacgtaaa 136140 ctttaatagt gcgaaatcat tcaaaaatct accacttata gatagatagt acataaatgc 136200 gtatagtagt ctacctatct ctttattatg aaaaccggca ttacgatcat atatgtcgtg 136260 atatacctgt gatccgttta cgttaaacca taaatacatg ggtgatccta taaacatgaa 136320 tttatttcta attctcagag ctatagttaa ttgaccgtgt aatatttgct tacatgcata 136380 cttgatacgc tcattaataa aatttttatc attgctcgtt atctcagaat cgtatatata 136440 aggagtacca tcgtgattct taccagatat tatacaaaat actatatata aaatatattg 136500 accaacgtta gtaatcatat aaatgtttaa cgttttaaat tttgtattca atgatccatt 136560 atcatacgct agcatggtct tatgatattc attctttaaa atataatatt gtgttagcca 136620 ttgcattggg gctcctaatg gagatttttt attctcatcc attttaggat aggctttcat 136680 aaagtcccta ataacttcgt gaataatgtt tctatgtttt ctactgatgc atgtatttgc 136740 ttcgattttt ttatcccatg tttcatctat catagattta aacgcagtaa tgctcgcaac 136800 attaacatct tgaaccgttg gtacaattcc gttccataaa tttataatgt tcgccattta 136860 tataactcat tttttgaata tacttttaat taacaaaaga gttaagttac tcatatgggc 136920 gccgtccagt ctgaacatca atctttttag ccagagatat catagccgct cttagagttt 136980 cagcgtgatt ttccaaccta aatagaactt catcgttgcg tttacaacac ttttctattt 137040 gttcaaactt tgttgttaca ttagtaatct ttttttccaa attagttagc cgttgtttga 137100 gagtttcctc attgtcgtct tcatcggctt taacaattgc ttcgcgttta gcctctggct 137160 ttttagcagc ctttgtagaa aaaaattcag ttgctggaat tgcaagatcg tcatctccgg 137220 ggaaaagagt tccgtccatt taaagtacag attttagaaa ctgacactct gcgttattta 137280 tatttggtac aacacatgga ttataaatat cgatgttaat aacatcagaa aatgtaaagt 137340 ctatacattg ttgcatcgtg ttaaattttc taatggatct agtattattg ggtccaactt 137400 ctgcctgaaa tccaaatatg gaagcggata caaaaccgtt tcctggataa accacacatc 137460 tccacttttg ctttacatca gaaattgtgt cgttgacatc ttgaactctc ctatctaatg 137520 ccggtgttcc acctatagat tttgaatatt cgaatgctgc atgagtagca ttaaattcct 137580 taatattgcc ataattttca tatattgagt aaccctggat aaaaagtaaa cacaccgcag 137640 ccgtcgctac cacaataaaa aaaattgata gagagttcat ttataatcta ttagaagctg 137700 acaaaatttt tttacacgca tcagacaatg ctttaataaa tagttcaaca tctacttttg 137760 tcatatcgaa ccgatggtat gattctaacc tagaattaca tccgaaaaag ttgactatgt 137820 tcatagtcat taagtcatta acaaacaaca ttccagactc tggattataa gacgatactg 137880 tttcgtcaca attacctacc ttaatcatgt gattatgaat attggctatt agagcacctt 137940 ctaagaaatc tataatatct ttgaaacacg atttaaaatc aaaccacgaa tatacttcta 138000 cgaagaaagt tagtttaccc ataggagaaa taactataaa tggagatcta aatacaaaat 138060 ccggatctat gatagtttta acattattat attctctatt aaatacctcc acatctaaaa 138120 atgttaattt tgaaactatg tcttcgttta ttaccgtacc tgaactaaac gctataagct 138180 ctattgtttg agaactcttt aaacgatatt cttgaaatac atgtaacaaa gtttccttta 138240 actcggtcgg tttatctacc atagttacag aatttgtatc cttatctata atataataat 138300 caaaatcgta taaagttata taattatcgc gttcagattg ggatcttttc aaatagacta 138360 aaaaccccat ttctctagta agtatcttat gtatatgttt gtaaaatatc ttcatggtgg 138420 gaatatgctc taccgcagtt agccattcct cattgacagc ggtagatgta ttagacaaaa 138480 ctattccaat gtttaacaag ggccatttta cgagattatt aaatccttgt ttgataaatg 138540 tagccaatga gggttcgagt tcaacgacga ttgaattctc ttccccgcgga tgctgcatga 138600 tgaacgacgg gatgttgttc gattgatttg gaattctttt tcgacttttt gtttatatta 138660 aatattttaa aatttatagc ggatagcaat tcatgtacca cggataatgt agacgcgtat 138720 tgcgcatcga tatctttatt attagataaa tttatcaata aatgtgagaa gtttgcctcg 138780 ttaaggtctt ccatttaaat attatataaa catttgtgtt tgtatcttt tcgtctttta 138840 tggaatagtt ttttactagt aaagctgcaa ttacacactt tgtccgtaaa acataaatat 138900 aaacaccagc ttttatcaat cgttccaaaa agtcgacggc ggacattttt aacatggcat 138960 ctattttaaa tacacttagg tttttggaaa aaacatcatt ttataattgt aacgattcaa 139020 taactaaaga aaagattaag attaaacata agggaatgtc atttgtattt tataagccaa 139080 agcattctac cgttgttaaa tacttgtctg gaggaggtat atatcatgat gatttggttg 139140 tattgggggaa ggtaacaatt aatgatctaa agatgatgct attttacatg gatttatcat 139200 atcatggagt gacaagtagt ggagcaattt acaaattggg atcgtctatc gatagacttt 139260 ctctaaatag gactattgtt acaaaagtta ataattatga tgatacattt tttgacgacg 139320 atgattgatc gctattgcac aattttgttt ttttactttc taatatagcg tttagattct 139380 ttttcatgtg cgaatattga tttactaaaa tatcgatgtt taacttttgt tctatgacgt 139440 ccttatcagc ggtatcggta catatacgta attcaccttc acaaaatacg gagtcttcga 139500 taataatagc caatcgatta ttggatctag cggtctgtat catattcaac atgtttaata 139560 tatcctttcg tttccccttt acaggcatcg atcgtagcat attttccgcg tctgagatgg 139620 aaatgttaaa actacaaaaa tgcgtaatgt tagcccgtcc taatattggt acgtgtctat 139680 aagtttggca tagtagaata atagacgtgt ttaaatgcct tccaaagttt aagaattcta 139740 ttagagtatt gcattttgat agtttatcgc ctacatcatc aaaaataagt aaaaagtgtg 139800 ctgatttttt atgattttgt gcgacagcaa tacatttttc tatgttactt ttagttcgta 139860 tcagattata ttctagagat tcctgactac taacgaaatt aatatgattt ggccaaatgt 139920 atccatcata atctggatta taaacgggtg taaacaagaa tatatgttta tattttttaa 139980 ctagtgtaga aaacagagat agtaaataga tagtttttcc agatccagat cctcccgtta 140040 aaaccattct aaacggcatt tttaataaat tttctcttga aaattgtttt tcttggaaac 140100 aattcataat tatatttaca gttactaaat taatttgata ataaatcaaa atatggaaaa 140160 ctaaggtcgt tagtagggag gagaacaaag aaggcacatc gtgacataaa taacatttat 140220 tatcatgatg acaccagaaa acgacgaaga gcagacatct gtgttctccg ctactgttta 140280 cagagacaaa attcagggaa agaataaacg caaacgcgtg attggtctat gtattagaat 140340 atctatggtt atttcactac tatctatgat taccatgtcc gcgtttctca tagtgcgcct 140400 aaatcaatgc atgtctgcta acgaggctgc tattactgac gccgctgttg ccgttgctgc 140460 tgcatcatct actcatagaa aggttgcgtc tagcactacg caatatgatc acaaagaaag 140520 ctgtaatggt ttatattacc agggttcttg ttatatatta cattcagact accagttat 140580 ctcggatgct aaagcaaatt gcactgcgga atcatcaaca ctacccaata aatccgatgt 140640 cttgactacc tggctcattg attatgttaa ggatacatgg ggatctgatg gtaatccaat 140700 tacaaaaact acatccgatt atcaagattc tgatgtatca caagaagtta gaaagtattt 140760 ttgtgttaaa acaatgaact aatatttatt tttgtacatt aataaatgaa atcgcttaat 140820 agacaaactg taagtaggtt taagaagttg tcggtgccgg ccgctataat gatgatactc 140880 tcaaccatta ttagtggcat aggaacattt ctgcattaca aagaagaact gatgcctagt 140940 gcttgcgcca atggatggat acaatacgat aaacattgtt atttagatac taacattaaa 141000 atgtctacag ataatgcggt ttatcagtgt cgtaaattac gagccagatt gcctagaccg 141060 gatactagac atctgagagt attgtttagt attttttata aagattattg ggtaagttta 141120 aaaaagacca atgataaatg gttagatatt aataatgata aagatataga tattagtaaa 141180 ttaacaaatt ttaaacaact aaacagtacg acggatgctg aagcgtgtta tatatacaag 141240 tctggaaaac tggttaaaac agtatgtaaa agtactcaat ctgtactatg tgttaaaaaa 141300 ttctacaagt gacaacaaaa aatgaattaa taataagtcg ttaacgtacg ccgccatgga 141360 cgccgcgttt gttattactc caatgggtgt gttgactata acagatacat tgtatgatga 141420 tctcgatatc tcaatcatgg actttatagg accatacatt ataggtaaca taaaaactgt 141480 ccaaatagat gtacgggata taaaatattc cgacatgcaa aaatgctact ttagctataa 141540 gggtaaaata gttcctcagg attctaatga tttggctaga ttcaacattt atagcatttg 141600 tgccgcatac agatcaaaaa ataccatcat catagcatgc gactatgata tcatgttaga 141660 tatagaagat aaacatcagc cattttatct attcccatct attgatgttt ttaacgctac 141720 aatcatagaa gcgtataacc tgtatacagc tggagattat catctaatca tcaatccttc 141780 agataatctg aaaatgaaat tgtcgtttaa ttcttcattc tgcatatcag acggcaatgg 141840 atggatcata attgatggga aatgcaatag taatttttta tcataaaagt tgtaaagtaa 141900 ataataaaac aataaatatt gaactagtag tacgtatatt gagcaatcag aaatgatgct 141960 ggtacctctt atcacggtga ccgtagttgc gggaacaata ttagtatgtt atatattata 142020 tatttgtagg aaaaagatac gtactgtcta taatgacaat aaaattatca tgacaaaatt 142080 aaaaaagata aagagttcta attccagcaa atctagtaaa tcaactgata gcgaatcaga 142140 ctgggaggat cactgtagtg ctatggaaca aaacaatgac gtagataata tttctaggaa 142200 tgagatattg gacgatgata gcttcgctgg tagtttaata tgggataacg aatccaatgt 142260 tatggcgcct agcacagaac acatttacga tagtgttgct ggaagcacgc tgctaataaa 142320 taatgatcgt aatgaacaga ctatttatca gaacactaca gtagtactta atgaagatac 142380 caaacagaat cctaactatt catccaatcc tttcgtaaat tataataaaa ccagtatttg 142440 tagcaagtca aatccgttca ttacagaact caacaataaa tttagtgaga ataatccgtt 142500 tagacgagca catagcgatg attatcttaa taagcaagaa caagatcatg aacacgatga 142560 tatagaatca ttggtgtgat tagtttcctt tttataaaat tgaagtaata tttagtatta 142620 ttgctgccgt cacgttgtac aaatggagat attccctgta ttcggcattt ctaaaattag 142680 caattattatt gctaataatg actgtagata ttatatagat acagaacatc aaaaaattat 142740 atctgatgag atcaatagac agatggatga aacggtactt cttaccaaca tcttaagcgt 142800 agaagttgta aatgacaatg agatgtacca tcttattcct catagattat cgacgattat 142860 actctgtatt agttctgtcg gaggatgtgt tatctctata gataatgacg tcaatggcaa 142920 aaatattcta acctttccca ttgatcatgc tgtaatcata tccccactga gtaaatgtgt 142980 cgtagttagc aagggtccta caaccatatt ggttgttaaa gcggatatac ctagcaaacg 143040 attggtaaca tcgtttacaa acgacatact gtatgtaaac aatctatcac tgattaatta 143100 tttgccgttg tctgtattca ttattagacg agttaccgac tatttggata gacacatatg 143160 cgatcagata tttgcgaata ataagtggta ttccattata accatcgaca ataagcagtt 143220 tcctattcca tcaaactgta taggtatgtc ctctgccaag tacataaatt ctagcatcga 143280 gcaagatact ttaatacatg tttgtaacct cgagcatcca ttcgacttag tatacaaaaa 143340 aatgcagtcg tacaattctg tacctatcaa ggaacaaata ttgtacggta gaattgataa 143400 tataaatatg agcattagta tttctgtgga ttaatagatt tctagtatgg ggatcattaa 143460 tcatctctaa tctctaaata cctcataaaa cgaaaaaaaa gctattatca aatactgtac 143520 ggaatggatt cattctcttc tctttttatg aaactctgtt gtatatctac tgataaaact 143580 ggaagcaaaa aatctgataa aaagaataag aataagatca aggattatta taaaataaca 143640 atagttcctg gttcctcttc cacgtctact agctcgtggt attatacaca tgcctagtaa 143700 tagtctcttt gcgttgacgg aaagcagact agaaataaca ggctaaaatg ttcagacacc 143760 ataatagttc ccaacccaga taataacaga gtaccatcaa cacattcctt taaactcaat 143820 cccaaaccca aaaccgttaa aatgtatccg gccaattgat agtagataat gaggtgtaca 143880 gcgcatgata atttacacag taaccaaaat gaaaatactt tagtaattat aagaaatata 143940 gatggtaacg tcatcatcaa caatccaata atatgccgga gagtaaacat tgacggataa 144000 aacaaaaatg ctccgcataa ctctatcatg gcaataacac aaccaaatac ttgtaagatt 144060 cctaaattag tagaaaatac aacggatatc gatgtataag tgatctcgag aaataataag 144120 aataaagtaa tgcccgtaaa gataaacatc aacattgttt ggtaatcatt aaaccaatta 144180 gtatgaagtt gaactaattt cacagtagat tttatccag tattatcccc gcatgtataa 144240 gtacctggta agatatcttt atattccata atcaatgaga catcactatc tgataacgaa 144300 tgaagtctag cactagtatg ccatttactt aatattgtcg tcttggaagt tttattataa 144360 gttaaaatat catggttatc caatttccat ctaatatact ttgtcggatt atctatagta 144420 cacggaataa tgatggtatc attacatgct gtatactcta tggtctttgt agttgttata 144480 acaaccaacg tatagaggta tatcaacgat attctaactc ttgacatttt ttatttattt 144540 aaaatgatac ctttgttatt tattttattc tattttgcta acggtattga atggcataag 144600 tttgaaacga gtgaagaaat aatttctact tacttattag acgacgtatt atacacgggt 144660 gttaatgggg cggtatacac attttcaaat aataaactaa acaaaactgg tttaactaat 144720 aataattata taacaacatc tataaaagta gaggatgcgg aaccaataac ggaaatccca 144780 aatgttggaa aatagacggt tcagacgacc caaaacatag aggtagagga tacgctcctt 144840 atcaaaatag caaagtaacg ataatcagtc acaacggatg tgtactatct gacataaaca 144900 tatcaaaaga agggaattaaa cgatggagaa gatttgacgg accatgtggt tatgatttat 144960 acacggcgga taacgtaatt ccaaaagatg gtttacgagg agcattcgtc gataaagatg 145020 gtacttatga caaagtttac attcttttca ctgatactat cggctcaaag agaattgtca 145080 aaattccgta tatagcacaa atgtgcctaa acgacgaagg tggtccatca tcattgtcta 145140 gtcatagatg gtcgacgttt ctcaaagtcg aattagaatg tgatatcgac ggaagaagtt 145200 atagacaaat tattcattct agaactataa aaacagataa tgatacgata ctatatgtat 145260 tcttcgatag tccttattcc aagtccgcat tatgtaccta ttctatgaat accattaaac 145320 aatctttttc tacgtcaaaa ttggaaggat atacaaagca attgccgtct ccagctcctg 145380 gtatatgttt accagctgga aaagttgttc cacataccac gtttgaagtc atagaaaaat 145440 ataatgtact agatgatatt ataaagcctt tatctaacca acctatcttc gaaggaccgt 145500 ctggtgttaa atggttcgat ataaaggaga aggaaaatga acatcgggaa tatagaatat 145560 acttcataaa agaaaattct atatattcgt tcgatacaaa atctaaacaa actcgtagct 145620 cgcaagtcga tgcgcgacta ttttcagtaa tggtaacttc gaaaccgtta tttatagcag 145680 atatagggat aggagtagga atgccacaaa tgaaaaaaat acttaaaatg taatcttaat 145740 cgagtacacc gcacgacaat gaacaaacat aagacagatt atgctggtta tgcttgctgc 145800 gtaatatgcg gtctaattgt tggaattatt tttacagcga cactattaaa agttgtagaa 145860 cgtaaattag ttcatacacc atcaatagat aaaacgataa aagatgcata tattagagaa 145920 gattgtccta ctgactggat aagctataat aataaatgta tccatttatc tactgatcga 145980 aaaaacctgg gaggaaggac gtaatgcatg caaagctcta aatccaaatt cggatctaat 146040 taagatagag actccaaacg agttaagttt tttaagaagc cttagacgag gctattgggt 146100 aggagaatcc gaaatattaa accagacaac cccatataat tttatagcta aaaatgccac 146160 gaagaatgga actaaaaaac ggaaatatat ttgtagtaca acgaatactc ccaaactgca 146220 ttcgtgttac actatataac aattacacta catttttatc ataacactac ttcggttaga 146280 tgttttagaa aaaaataaat atcgccgtac cgttcttgtt tttataaaaa taacaattaa 146340 caattatcaa atttttctt taatatttta cgtggttgac cattcttggt ggtaaaataa 146400 tctcttagtg ttggaatgga atgctgttta atgtttccgc actcatcgta tattttgacg 146460 tatgcagtca catcgtttac gcaatagtca gactgtagtt ctatcatgct tcctacatca 146520 gaaggagggaa cagttttaaa gtctcttggt tttaatctat tgccattagt tttcatgaaa 146580 tcctttgttt tatccacttc acattttaaa taaatgtcca ctatacattc ttctgttaat 146640 tttactagat cgtcatgggt catagaattt ataggttccg tagtccatgg atccaaacta 146700 gcaaacttcg cgtatacggt atcgcgatta gtgtataacac caactgtatg aaaattaaga 146760 aaacagttta ataaatcaac agaaatattt aatcctccgt ttgatacaga tgcgccatat 146820 ttatggattt cggattcaca cgttgtttgt ctgaggtgtt cgtctagtgt tgcttctacg 146880 taaacttcga ttcccatata ttctttattg tcagaatcgc ataccgattt atcatcatac 146940 actgtttgaa aactaaatgg tatacacatc aaaataataa ataataacga gtacattctg 147000 caatattgtt atcgtaattg gaaaattagt gttcgagtga gtcggattat gtgagtactg 147060 gattgtatat tttattttat attttgtaat aagaataaaa tgctaatgtc aagttattc 147120 caatagatgt cttattaaaa aacatatata ataaataaca atggctgaat ggcataaaat 147180 tatcgaggat atctcaaaaa ataataagtt cgaggatgcc gccatcgttg attacaagac 147240 tacaaagaat gttctagctg ctattcctaa cagaacattt gccaagatta atccgggtga 147300 aattattcct ctcatcacta atcgtaatat tctaaaacct cttattggtc agaaatattg 147360 tattgtatat actaactctc taatggatga gaacacgtat gctatggagt tgcttactgg 147420 gtacgcccct gtatctccga tcgttatagc gagaactcat accgcactta tatttttgat 147480 gggtaagcca acaacatcca gacgtgatgt gtatagaacg tgtagagatc acgctacccg 147540 tgtacgcgca actggtaatt aaaataaaaa gtaatattca tatgtagtgt caattttaaa 147600 tgatgatgat gaaatggata atatccatat tgacgatgtc aataatgccg gtattggcat 147660 acagctcatc gatttttaga tttcattcag aggatgtgga attatgttat gggcatttgt 147720 attttgatag gatctataat gtagtaaata taaaatataa tccgcatatt ccatatagat 147780 ataattttat taatcgcacg ttaaccgtag atgaactaga cgataatgtc ttttttacac 147840 atggttatttttaaaacac aaatatggtt cacttaatcc tagtttgatt gtctcattat 147900 caggaaactt aaaatataat gatatacaat gctcagtaaa tgtatcgtgt ctcattaaaa 147960 atttggcaac gagtacatct actatattaa catctaaaca taagacttat tctctacatc 148020 ggtccacgtg tattactata ataggatacg attctattat atggtataaa gatataaatg 148080 acaagtataa tgacatctat gattttactg caatatgtat gctaatagcg tctacattga 148140 tagtgaccat atacgtgttt aaaaaaataa aaatgaactc ttaattatgc tatgctatta 148200 gaaatggata aaatcaaaat tacggttgat tcaaaaattg gtaatgttgt taccatatcg 148260 tataacttgg aaaagataac tattgatgtt acacctaaaa agaaaaaaga aaaggatgta 148320 ttattagcgc aatcagttgc tgtcgaagag gcaaaagatg tcaaggtaga agaaaaaaat 148380 attatcgata ttgaagatga cgatgatatg gatgtagaaa gcgcataata cgatctataa 148440 aaataagtat ataataaata cttttattt acggtactct tgtagtggtg ataccctact 148500 caattatttt tttaaaaaaa tacttattct gattcttcta gccatttccg tgttcgttcg 148560 aatgccacat cgacgttaaa gataggggag tagttgaaat ctagttctgc attgttggta 148620 cgcacctcaa atgtagtgtt ggatatcttc aacgtatagt tgttgagtag tgatggtttt 148680 ctaaatagaa ttctcttcat atcattcttg cacgcgtaca tttttagcat ccatcttgga 148740 attctagatc cttgttctat tcccaatggt ttcatcaata gaagattaaa catatcgtac 148800 gaacacgatg gagagtaatc gtagcaaaag taagcatttc ctttaatctt agatcccgga 148860 tactggatat attttgcagc caacacgtgc atccatgcag catttcctac atatacccgg 148920 ctatgcaccg cgtcatcatc gactgtacga tacataatgt taccgtgttg cttcattgc 148980 tcgtaaaaga ctttcgtcaa tttgtctcct tctccgtaaa ttccagtggg tcttaggcaa 149040 caagtataca attttgctcc attcatgatt acggaattat tggctttcat aaccagttgc 149100 tcggccatac gtttactttt tgcgtataca tgtcctggtg atatatcata aagggtatgc 149160 tcatggccga tgaatggatc accgtgttta ttgggtccta ttgcttccat gctactagta 149220 tagatcaaat acttgattcc taggtccaca caagctgcca atatagtctg tgttccataa 149280 tagtttactt tcatgatttc attatcggtg tattttccaa atacatccac tagagcagcc 149340 gtatgaataa tcagatttac cccatctagc gcttctctca ccttatcaaa gtcgtttata 149400 tcacattgta tatagtttat aaccttaact ttcgaggtta ttggttgtgg atcttctaca 149460 atatctatga ctctgatttc ttgaacatca tctgcactaa ttaacagttt tactatatac 149520 ctgcctagaa atccggcacc accagtaacc gcgtacacgg ccattgctgc cactcataat 149580 atcagactac ttattctatt ttactaaata atggctgttt gtataataga ccacgataat 149640 atcagaggag ttatttactt tgaaccagtc catggaaaag ataaagtttt aggatcagtt 149700 attggattaa aatccggaac gtatagtttg ataattcatc gttacggaga tattagtcaa 149760 ggatgtgatt ccataggcag tccagaaata tttatcggta acatctttgt aaacagatat 149820 ggtgtagcat atgtttattt agatacagat gtaaatatat ttacaattat tggaaaggcg 149880 ttatctattt caaaaaatga tcagagatta gcgtgtggag ttattggtat ttcttacata 149940 aatgaaaaga taatacattt tcttacaatt aacgagaatg gcgtttgata tatcagttaa 150000 tgcgtctaaa acaataaatg cattagttta cttttctact cagcaaaata aattagtcat 150060 acgtaatgaa gttaatgata cacactacac tgtcgaattt gatagggaca aagtagttga 150120 cacgtttatt tcatataata gacataatga caccatagag ataagagggg tgcttccaga 150180 ggaaactaat attggttgcg cggttaatac gccggttagt atgacttact tgtataataa 150240 gtatagtttt aaactgattt tagcagaata tataagacac agaaatacta tatccggcaa 150300 tatttattcg gcattgatga cactagatga tttggctatt aaacagtatg gagacattga 150360 tctattattt aatgagaaac ttaaagtaga ctccgattcg ggactatttg actttgtcaa 150420 ctttgtaaag gatatgatat gttgtgattc tagaatagta gtagctctat ctagtctagt 150480 atctaaacat tgggaattga caaataaaaa gtataggtgt atggcattag ccgaacatat 150540 atctgatagt attccaatat ctgagctatc tagactacga tacaatctat gtaagtatct 150600 acgcggacac actgagagca tagaggatga atttgattat tttgaagacg atgattcgtc 150660 tacatgttct gccgtaaccg acagggaaac ggatgtataa ttttttttat agcgtgaagg 150720 atatgataaa aaatataatt gttgtattta tcccattcca atcaccttat atgattctgt 150780 aaaaaaatta tactgtaaca caataaagga gtcttataga tgtatagagg tcagatactg 150840 gtttgataaa ctgtttattc cacataagta tgtttgactt tatggttaga cccgcatact 150900 ttaacaaatc actgaaaatt ggagttaggt attgacctct cagaatcagt tgccgttctg 150960 gaacattaaa tgtatttttt atgatatact ccaacgcatt tatgtgggca tacaacaagt 151020 cattactaat ggagtattcc aagagtttta gttgtctagt atttaacaag agaagagatt 151080 tcaacagact gtttatgaac tcgaacgccg cctcattgtc gcttatattg atgatgtcga 151140 attctcccaa tatcatcact gatgagtagc tcatcttgtt atcgggatcc aagttttcta 151200 aagatgtcat taaaccctcg atcatgaatg gatttatcat catcgttttt atgttggaca 151260 tgagcttagt ccgtttgtcc acatctatag acgacgattt ctgaattatt tcatatatcc 151320 ctctctttaa ctccaggaac ttgtcaggat ggtctacttt aatatgttct cgtctaagag 151380 atgaaaatct ttggatggtt gcacgcgact tttctttaaa ggatgacgtt gcccaagatc 151440 ctctcttaaa tgaatccatc ttatccttgg acaagatgga cagtctattt tccttagatg 151500 gtttaatatt tttgttaccc atgatctata aaggtagacc taatcgtctc ggatgaccat 151560 atatttattt tcagttttat tatacgcata aattgtaaaa aatatgttag gtttacaaaa 151620 atgtctcgtg gggcattaat cgtttttgaa ggattggaca aatctgggaaa aacaacacaa 151680 tgtatgaaca tcatggaatc tataccggca aacacgataa aatatcttaa ctttcctcag 151740 agatccactg tcactggaaa gatgatagat gactatctaa ctcgtaaaaa aacctataat 151800 gatcatatag ttaatctatt attttgtgca aatagatggg agtttgcatc ttttatacaa 151860 gaacaactag aacagggaat tactttaata gttgatagat acgcattttc tggagtagcg 151920 tatgccgccg ctaaaggcgc gtcaatgact ctcagtaaga gttatgaatc tggattgcct 151980 aaacccgact tagttatatt cttggaatct ggtagcaaag aaattaatag aaacgtcggc 152040 gaggaaattt atgaagatgt tacattccaa caaaaggtat tacaagaata taaaaaaatg 152100 attgaagaag gagatattca ttggcaaatt atttcttctg aattcgagga agatgtaaag 152160 aaggagttga ttaagaatat agttatagag gctatacaca cggttactgg accagtgggg 152220 caactgtgga tgtaatagtg aaattacatt ttttataaat agatgttagt acagtgttat 152280 aaatggatga agcatattac tctggcaact tggaatcagt actcggatac gtgtccgata 152340 tgcataccga actcgcatca atatctcaat tagttatgc caagatagaa actatagata 152400 atgatatatt aaacaaggac attgtaaatt ttatcatgtg tagatcaaac ttggataatc 152460 catttatctc tttcctagat actgtatata ctattataga tcaagagatc tatcagaccg 152520 aattgattaa ttcattagac gacaatgaaa ttatcgattg tatagttaac aagtttatga 152580 gcttttataa ggataaccta gaaaatatag tagatgctat cattactcta aaatatataa 152640 tgaataatcc agattttaaa actacgtatg ccgaagtact cggttccaga atagccgata 152700 tagatattaa acaagtgata cgtaagaata tactacaatt gtctaatgat atccgcgaac 152760 gatatttgtg aaaaatatta aaaaaaaata ctttttttat taaatgacgt cgcttcgcga 152820 atttagaaaa ttatgctgtg atatatatca cgcatcagga tataaagaaa aatctaaatt 152880 aattagagac tttataacag atagggatga taaatatttg atcattaagc tattgcttcc 152940 cggattagac gatagaattt ataacatgaa cgataaacaa attataaaat tatatagtat 153000 aatatttaaa caatctcagg aagatatgct acaagattta ggatacggat atataggaga 153060 cactattagg actttcttca aagagaacac agaaatccgt ccacgagata aaagcatttt 153120 aactttagaa gaagtggata gttttttaac tacgttatca tccgtaacta aagaatcgca 153180 tcaaataaaa ttattgactg atgtagcatc tgtttgtaca tgtaatgatt taaaatgtgt 153240 agtcatgctt attgataaag atctaaaaat taaagcgggc cctcggtacg tacttaacgc 153300 tattagtcct catgcctatg atgtgtttag aaaatctaat aacttgaaag agataataga 153360 aaatgcatct aaacaaaatc tagactctat atctatttct gttatgactc caattaatcc 153420 catgttagcg gaatcgtgg attctgtcaa taaggcgttt aaaaaatttc catcaggaat 153480 gtttgcggaa gtcaaatacg atggtgaaag agtacaagtt cataaaaata ataacgagtt 153540 tgccttcttt agtagaaaca tgaaaccagt actctctcat aaagtggatt atctcaaaga 153600 atacataccg aaagcattta aaaaagctac gtctatcgta ttggattctg aaattgttct 153660 tgtagacgaa cataatgtac cgctaccgtt tggaagttta ggaatacaca aaaagaaaga 153720 atataaaaac tctaacatgt gtttgttcgt gtttgactgt ttgtactttg atggattcga 153780 tatgacggac attccattgt acgaacgaag atcttttctc aaagatgtta tggttgaaat 153840 acccaataga atagtattct cagagttgac gaatattagt aacgagtctc agttaactga 153900 cgtattggat gatgcactaa cgagaaaatt agaaggattg gtcttaaaag atattaatgg 153960 agtatacgaa ccgggaaaga gaagatggtt aaaaataaag cgagactatt tgaacgaggg 154020 ttccatggca gattctgccg atttagtagt actaggtgcc tactatggta aaggagcaaa 154080 gggtggtatc atggcagtct ttctaatggg ttgttacgac gatgaatccg gtaaatggaa 154140 gacggttacc aagtgttcag gacacgatga taatacgtta agggagttgc aagaccaatt 154200 aaagatgatt aaaattaaca aggatcccaa aaaaattcca gagtggttag tagttaataa 154260 aatctatatt cccgattttg tagtagagga tccgaaacaa tctcagatat gggaaatttc 154320 aggagcagag tttacatctt ccaagtccca taccgcaaat ggaatatcca ttagatttcc 154380 tagatttact aggataagag aggataaaac gtggaaagaa tctactcatc taaacgattt 154440 agtaaacttg actaaatctt aatagttaca tacaaactga aaattaaaat aacaccattt 154500 agttggtggt cgccatggat ggtgttattg tatactgtct aaacgcgtta gtaaaacatg 154560 gcgaggaaat aaatcatata aaaaatgatt tcatgattaa accatgttgt gaaagagttt 154620 gtgaaaaagt caagaacgtt cacattggcg gacaatctaa aaacaataca gtgattgcag 154680 atttgccata tatggataat gcggtatccg atgtatgcaa ttcactgtat aaaaagaatg 154740 tatcaagaat atccagattt gctaatttga taaagataga tgacgatgac aagactccta 154800 ctggtgtata taattatttt aaacctaaag atgttattcc tgttatcata tctataggaa 154860 aggataaaga tgtctgtgaa ctattaatct catcagacat atcgtgtgca tgcgtggagt 154920 taaattcata tcacgtagcc attcttccca tgaatgtttc cttttttacc aaaggaaatg 154980 cctcgttgat tattctcctg tttgatttct ctatcgatgc agcacctctc ttaagaagtg 155040 taaccgataa taatgttatt atatctagac accagcgtct acatgacgag cttccgagtt 155100 ccaattggtt caagttttac ataagtataa agtccgacta ttgttctata ttatatatgg 155160 ttgttgatgg atctgtgatg catgcgatag ctgataatag aactcacgca attattagca 155220 aaaatatatt agacaatact acaattaacg atgagtgtag atgctgttat tttgaaccac 155280 agattaggat tcttgataga gatgagatgc tcaatggatc atcgtgtgat atgaacagac 155340 attgtattat gatgaattta cctgatgtag gcgaatttgg atctagtatg ttggggaaat 155400 atgaacctga catgattaag attgctcttt cggtggctgg taatttaata agaaatcgag 155460 actacattcc cgggagacga ggctatagct actacgttta cggtatagcc tctagataat 155520 ttttttaagc acgaaataaa aaacataatt ttaaaccaat ctatttcata ctattttggg 155580 tgatcaccat ggacataaag atagatatta gtatttctgg tgataaattt acggtgacta 155640 ctaggaggga aaatgaagaa agaaaaaaat atctacctct ccaaaaagaa aaaactactg 155700 atgttatcaa acctgattat cttgagtacg atgacttgtt agatagagat gagatgttta 155760 ctattctaga ggaatatttt atgtacagag gtctattagg cctcagaata aaatatggac 155820 gactctttaa cgaaattaaa aaattcgaca atgatgcgga agaacaattc ggtactatag 155880 aagaactcaa gcagaaactt agattaaatt ctgaagaggg agcagataac tttatagatt 155940 atataaaggt acaaaaacag gatatcgtca aacttactgt atacgattgc atatctatga 156000 taggattgtg tgcatgcgtg gtagatgttt ggagaaatga gaaactgttt tctagatgga 156060 aatattgttt acgagcgatt aaactgttta ttaatgatca catgcttgat aagataaaat 156120 ctatactgca gaatagacta gtatatgtgg aaatgtcata gaaagttaat gagagcaaaa 156180 atatataagg ttgtattcca tatttgttat tttttctgta atagttaaaa aaatacattc 156240 gatggtctat ctatcagatt attatgtgtt ataaggtact ttttctcata ataaactaga 156300 gtatgagtaa gatagtgttt ttcaaaacat ataaatctaa aattgatgga tgagatatac 156360 agctattaat ttcgaaaata tataaatcta aaattgatgg ataagatata cagctattaa 156420 tttcgaaaat atattttaat ctgataactt taaacatgga tttttgatgg tggtttaacg 156480 ttttaaaaaa agattttgtt attgtagtat atgataatat taaaagatgg atataaagaa 156540 tttgctgact gcatgtacta ttttttacat tactacattg gctacggcag atatacctac 156600 tccgccacca acgggtcatg tgacaaggga gaatatcttg ataagaggca taatcaatgt 156660 tgtaatcggt gtccacctgg agaatttgcc aaggttagat gtaatggtaa cgataacaca 156720 aaatgtgaac gctgcccacc tcatacatat accacaatcc ccaattattc taatggatgt 156780 catcaatgta gaaaatgccc aaccggatca tttgataagg taaagtgtac cggaacacag 156840 aacagtaaat gttcgtgtct tcctggttgg tattgcgcta ctgattcttc acagactgaa 156900 gattgttgaa attgtgtacc aaaaaggaga tgtccatgcg gatactttgg tggaatagat 156960 gaacaaggaa atcctatttg taaatcgtgc tgtattggtg aatattgcaa ctacctacgt 157020 aattatagac ttgatccatt ttctccatgc aaactatcta aatgtaatta attatgattt 157080 tgatgataat gttaccatac attatatcgc tacttggtta gtgtattatt cagtatgaag 157140 acctattaat aattacttat cttttgacga tcttgttata attataatat aaaaacttat 157200 ggcatagtaa ctcataattg ctgacgcgat aaattcgtaa taatctgttt tgttcaaatt 157260 tttataagga atctacaggc ataaaaataa aaatataatt tataatatac tcttacagcg 157320 cgccatcatg aatagcagca gtaaattaat tgctgtatt aatggattta gaaatagtgg 157380 acgattttgt gatattaata tagttattaa tgatgaaagg ataaacgctc acagactcat 157440 cctatctgga gcctccgaat atttttccat tctgttttcc aataatttta tcgattctaa 157500 tgaatacgaa gttaatctaa gtcatttaga ttatcaaagt gttaacgatt tgatcgatta 157560 catttatgggg atacctttga gcctaactaa cgataacgtg aaatatattc tttcaaccgc 157620 tgatttttta caaattggat ctgccattac tgagtgcgaa aaatacatac ttaaaaatct 157680 ttgttctaga aactgtatcg atttctacat atacgctgat aaatataata acaagaaaat 157740 agaatcagcg tcgtttaaca caatattacg aaatattttg agactcatca acgatgaaaa 157800 ctttaaatac ttaacagagg aatcaatgat aaaaatttta agcgatgata tgttaaatat 157860 aaaaaatgag gattttgcac cactaattct cattaaatgg ttagagagta ctcaacaatc 157920 atgcaccgtc gagttactta gatgcctcag aatatcattg ctttccccac aagttataaa 157980 atcactttat agtcatcaac tggttagttc aatctacgaa tgtataacat tcttaaacaa 158040 tatagcattc ttggatgaat catttcctag ataccatagc atcgagttga tatctatcgg 158100 tataagtaat tcgcatgata agatttccat aaactgctac aatcataaaa aaaatacatg 158160 ggaaatgata tcttcacgta gatataggtg tagtttcgca gtggccgtcc tggataatat 158220 tatctatatg atgggtggat atgatcagtc cccgtataga agttcaaagg ttatagcgta 158280 caatacatgt acaaattctt ggatatatga tataccagag ctaaaatatc ctcgttctaa 158340 ttgtggggga ctggctgatg acgaatacat ttattgtata ggcggcatac gcgatcagga 158400 ttcatcgttg acatctagta ttgatagatg gaagccatca aaaccatatt ggcagaagta 158460 tgctaaaatg cgcgaaccaa aatgtgatat gggggttgcg atgttaaacg gattaatata 158520 tgtcatgggt ggaatcgtta aaggtgacac gtgtaccgac gcactagaga gtttatcaga 158580 agatggatgg atgaagcatc aacgtcttcc aataaaaatg tccaatatgt cgacgattgt 158640 tcatgatggc aagatttata tatctggagg ttacaacaat agtagtgtag ttaatgtaat 158700 atcgaatcta gtccttagct ataatccgat atatgatgaa tggaccaaat tatcatcatt 158760 aaacattcct agaattaatc ccgctctatg gtcagcgcat aataaattat atgtaggagg 158820 aggaatatct gatgatgttc gaactaatac atctgaaaca tacgataaag aaaaagattg 158880 ttggacattg gataatggtc acgtgttacc acgcaattat ataatgtata aatgcgaacc 158940 gattaaacat aaatatccat tggaaaaaac acagtacacg aatgattttc taaagtattt 159000 ggaaagtttt ataggtagtt gatagaacaa aatacataat tttgtaaaaa taaatcactt 159060 tttatactaa tatgacacga ttaccaatac ttttgttact aatatcatta gtatacgcta 159120 caccttttcc tcagacatct aaaaaaatag gtgatgatgc aactctatca tgtaatcgaa 159180 ataatacaaa tgactacgtt gttatgagtg cttggtataa ggagcccaat tccattattc 159240 ttttagctgc taaaagcgac gtcttgtatt ttgataatta taccaaggat aaaatatctt 159300 acgactctcc atacgatgat ctagttacaa ctatcacaat taaatcattg actgctagag 159360 atgccggtac ttatgtatgt gcattcttta tgacatcaac tacaaatgac actgataaag 159420 tagattatga agaatactcc acagagttga ttgtaaatac agatagtgaa tcgactatag 159480 acataatact atctggatct acacattcac cagaaactag ttctgagaaa ccagaggata 159540 tagataattt taattgctcg tcggtattcg aaatcgcgac tccggaacca attactgata 159600 atgtagaaga tcatacagac accgtcacat acactagtga tagcattaat acagtaagtg 159660 catcatctgg agaatccaca acagacgaga ctccggaacc aattactgat aaagaagaag 159720 atcatacagt cacagacact gtctcataca ctacagtaag tacatcatct ggaattgtca 159780 ctactaaatc aaccaccgat gatgcggatc tttatgatac gtacaatgat aatgatacag 159840 taccaccaac tactgtaggc ggtagtacaa cccttatag caattataaa accaaggact 159900 ttgtagaaat atttggtatt accgcattaa ttatattgtc ggccgtggca atattctgta 159960 ttacatatta tatatataat aaacgttcac gtaaatacaa aacagagaac aaagtctaga 160020 tttttgactt acataaatgt ctgggatagt aaaatctatc atattgagcg gaccatctgg 160080 ttcaggaaag acagccatag ccaaaagact atgggaatat atttggattt gtggtgtccc 160140 ataccactag atttcctcgt cctatggaac gagaaggtgt cgattaccat tacgttaaca 160200 gagaggccat ctggaaggga atagccgccg gaaactttct agaacatact gagtttttag 160260 gaaatattta cggaacttct aaaactgctg tgaatacagc ggctattaat aatcgtattt 160320 gtgtgatgga tctaaacatc gatggcgtta gaagtcttaa aaatacgtac ctaatgcctt 160380 actcggtgta tataagacct acctctctta aaatggttga gaccaagctt cgttgtagaa 160440 acactgaagc ggatgatgag attcatcgtc gtgtgatgtt ggcaaaaact gacatggatg 160500 aggcaggtga agccggtcta ttcgacacta ttatcattga agatgatggg aatttagcat 160560 atagtaagtt aattcagata ctacaggacc gtattagaat gtattttaac actaattaga 160620 gacttaagac ttaaaacttg ataattaata atataactcg tttttatatg tggctatttc 160680 aacgtctaat gttagtta aatattaaaa cttaccacgt aaaacttaaa atttaaaatg 160740 atatttcatt gacagataga tcacacatta tgaactttca aggacttgtg ttaactgaca 160800 attgcaaaaa tcaatgggtc gttggaccat taataggaaa aggtggattc ggtagtattt 160860 atactactaa tgacaataat tatgtagtaa aaatagagcc caaagctaac ggatcattat 160920 ttaccgaaca ggcattttat actagagtac ttaaaccatc cgttatcgaa gaatgggaaaa 160980 aatctcacaa tataaagcac gtaggtctta tcacgtgcaa ggcatttggt ctatacaaat 161040 ccattaatgt ggaatatcga ttcttggtaa ttaatagatt aggtgcagat ctagatgcgg 161100 tgatcagagc caataataat agattaccaa aaaggtcggt gatgttgatc ggaatcgaaa 161160 tcttaaatac catacaattt atgcacgagc aaggatattc tcacggagat attaaagcga 161220 gtaatatagt cttggatcaa atagataaga ataaattata tctagtggat tacggattgg 161280 tttctaaatt catgtctaat ggcgaacatg ttccatttat aagaaatcca aataaaatgg 161340 ataacggtac tctagaattt acacctatag attcgcataa aggatacgtt gtatctagac 161400 gtggagatct agaaacactt ggatattgta tgattagatg gttgggaggt atcttgccat 161460 ggactaagat atctgaaaca aagaattgtg cattagtaag tgccacaaaa cagaaatatg 161520 ttaacaatac tgcgactttg ttaatgacca gtttgcaata tgcacctaga gaattgctgc 161580 aatatattac catggtaaac tctttgacat attttgagga acccaattac gacgagtttc 161640 ggcacatatt aatgcagggt gtatattatt aagtgtggtg tttggtcgat gtaaaatttt 161700 tgtcgataaa aattaaaaaa taacttaatt tattattgat ctcgtgtgta caaccgaaat 161760 catggcgatg ttttacgcac acgctctcgg tgggtacgac gagaatcttc atgcctttcc 161820 tggaatatca tcgactgttg ccaatgatgt caggaaatat tctgttgtgt cagtttataa 161880 taacaagtat gacattgtaa aagacaaata tatgtggtgt tacagtcagg tgaacaagag 161940 atatattgga gcactgctgc ctatgtttga gtgcaatgaa tatctacaaa ttggagatcc 162000 gatccatgat caagaaggaa atcaaatctc tatcatcaca tatcgccaca aaaactacta 162060 tgctctaagc ggaatcgggt acgagagtct agacttgtgt ttggaaggag tagggattca 162120 tcatcacgta cttgaaacag gaaacgctgt atatggaaaa gttcaacatg attattctac 162180 tatcaaagag aaggccaaag aaatgaatgc actcagttca ggacctatca tcgattacca 162240 cgtctggata ggagattgta tctgtcaagt tactgctgtg gacgtacatg gaaaggaaat 162300 tatgagaatg agattcaaaa agggtgcggt gctacagatc ccaaatctgg taaaagttaa 162360 acttggggag aatgatacag aaaatctttc ttctactata tcggcggcac catcgaggta 162420 accacctctc aagaagaccg cgtgaataat gtactcatga aacgtttgga aactatacgc 162480 catatgtggt ctgttgtata tgatcatttt gatattgtga atggtaaaga atgctgttat 162540 gtgcatacgc attcatctaa tcaaaatcct ataccgagta ctgtaaaaac aaatttgtac 162600 atgaagacta tgggatcatg cattcaaatg gattccatgg aagctctaga gtatcttagc 162660 gaactgaagg aatcaggtgg atggagtccc agaccagaaa tgcaggaatt tgaatatcca 162720 gatggagtgg aagacactga atcaattgag agattggtag aggagttctt caatagatca 162780 gaacttcagg ctggtaaatt agtcaaattt ggtaattcta ttaattgtta aacatacatc 162840 tgtttcagct aagcaactaa gaacacgtat acggcagcag cttcctttta tactctcatc 162900 ttttaccaac acaaagggtg gatatttgtt cattggagtt gataataata cacacaaagt 162960 atttggattc acggtgggtt acgactacct cagactgata gagaatgata tagaaaagca 163020 tatcaaaaga ctttgtgttg tgcatttctg tgagaagaaa gaggacatca agtacacgtg 163080 tcgattcatc aaggtatata aacctgggga tgaggctacc tcgacatacg tgtgcgctat 163140 caaagtgggaa agatgctgtt gtgctgtgtt tgcagattgg ccagaatcat ggtatatgga 163200 tactaatggt atcaagaagt attctccaga tgaatgggtg tcacatataa aattttaatt 163260 aatgtaacta tagagaacaa ataataggtt gtaatatcat atagacaata actaacaatt 163320 aattagtaac tgttatctct tttttaacta accaactaac tatataccta ttaatacatc 163380 gtaattatag ttcttaacat ctattaatca ttgattcgct tctttaattt tttataaact 163440 aacattgtta attgaaaagg gataacatgt tacagaatat aaattatata tggatttttt 163500 taaaaaggaa atacttgact ggaggtgtata tttatctctt cattatatag cacgcgtgtg 163560 ttccaattct tccacatccc atataataca ggattataat ctcgttcgaa catacgagaa 163620 agtggataaa acaatagttg attttttatc taggttgcca aatttattcc atattttaga 163680 atatgggggaa aatattctac atatttattc tatggatgat gctaatacga atattataat 163740 tttttttcta gatagagtat taaatattaa taagaacggg tcatttatac acaatctcag 163800 gttatcatca tccattaata taaaagaata tgtatatcaa ttagttaata atgatcatcc 163860 agataatagg ataagactaa tgcttgaaaa tggacgtaga acaagacatt ttttgtccta 163920 tatatcagat acagttaata tctatatatg tattttaata aatcatggat tttatataga 163980 tgcagaagac agttacggtt gtacattatt acatagatgt atatatcact ataagaaatc 164040 agaatcagaa tcatacaatg aattaattaa gatattgtta aataatggat ccgatgtaga 164100 taaaaaagat acgtacggaa acacaccttt tatcctatta tgtaaacacg atatcaacaa 164160 cgtggaattg tttgagatat gtttagagaa tgctaatata gactctgtag actttaatag 164220 atatacacct cttcattatg tctcatgtcg taataaatat gattttgtaa agttattaat 164280 ttctaaagga gcaaatgtta atgcgcgtaa taaattcgga actactccat tttatgtgg 164340 aattatacac ggtatctcgc ttataaaact atatttggaa tcagacacag agttagaaat 164400 agataatgaa catatagttc gtcatttaat aatttttgat gctgttgaat ctttagatta 164460 tctattatcc agaggagtta ttgatattaa ctatcgtact atatacaacg aaacatctat 164520 ttacgacgct gtcagttata atgcgtataa tacgttggtc tatctattaa acagaaatgg 164580 tgattttgag acgattacta ctagtggatg tacatgtatt tcggaagcag tcgcaaacaa 164640 caacaaaata ataatggaag tactattgtc taaacgacca tctttgaaaa ttatgataca 164700 gtctatgata gcaattacta aaaataaaca acataatgca gatttattga aaatgtgtat 164760 aaaatatact gcgtgtatga ccgattatga tactcttata gatgtacagt cgctacagca 164820 atataaatgg tatattttaa aatgtttcga tgaaatagat atcatgaaga gatgtttatat 164880 aaaaaataaa actgtattcc aattagtttt ttgtatcaaa gacattaata ctttaatgag 164940 atatggtaaa catccttctt tcgtgaagtg cactagtctc gacgtatacg gaagtcgtgt 165000 acgtaatatc atagcatcta ttagatatcg tcagagatta attagtctat tatccaagaa 165060 gctggatgcg ggagataaat ggtcgtgttt tcctaacgaa ataaaatata aaatattgga 165120 aaactttaac gataacgaac tatccacata tctaaaaatc ttataaacac tattaaaata 165180 taaaatctaa gtaggataaa atcacactac atcattgttt ccttttagtg ctcgacagtg 165240 tatactattt ttaacactca taaataaaaa tgaaaacgat ttccgttgtt acgttgttat 165300 gcgtactacc tgctgttgtt tattcaacat gtactgtacc cactatgaat aacgctaaat 165360 taacgtctac cgaaacatcg tttaatgata aacagaaagt tacatttaca tgtgatcagg 165420 gatatcattc tttggatcca aatgctgtct gcgaaacaga taaatggaaa tacgaaaatc 165480 catgcaagaa aatgtgcaca gtttctgatt atgtctctga attatatgat aagccattat 165540 acgaagtgaa ttccaccatg acactaagtt gcaacggcga aacaaaatat tttcgttgcg 165600 aagaaaaaaa tggaaatact tcttggaatg atactgttac gtgtcctaat gcggaatgtc 165660 aacctcttca attagaacac ggatcgtgtc aaccagttaa agaaaaatac tcatttgggg 165720 aatatatgac tatcaactgt gatgttggat atgaggttat tggtgcttcg tacataagtt 165780 gtacagctaa ttcttggaat gttattccat catgtcaaca aaaatgtgat ataccgtctc 165840 tatctaatgg attaatttcc ggatctacat tttctatcgg tggcgttata catcttagtt 165900 gtaaaagtgg ttttatacta acgggatctc catcatccac atgtatcgac ggtaaatgga 165960 atcccatact cccaacatgt gtacgatcta acgaaaaatt tgatccagtg gatgatggtc 166020 ccgacgatga gacagatttg agcaaactct cgaaagacgt tgtacaatat gaacaagaaa 166080 tagaatcgtt agaagcaact tatcatataa tcatagtggc gttaacaatt atgggcgtca 166140 tatttttaat ctccgttata gtattagttt gttcctgtga caaaaataat gaccaatata 166200 agttccataa attgctaccg taaatataaa tccgttaaaa taattaataa tttaataaca 166260 aacaagtatc aaaagattaa agacttatag ctagaatcaa ttgagatgtc ttcttcagtg 166320 gatgttgata tctacgatgc cgttagagca tttttactca ggcactatta taacaagaga 166380 tttatgtgt atggaagaag taacgccata ttacataata tatacaggct atttacaaga 166440 tgcgccgtta taccgttcga tgatatagta cgtactatgc caaatgaatc acgtgttaaa 166500 caatgggtga tggatacact taatggtata atgatgaatg aacgcgatgt ttctgtaagc 166560 gttggcaccg gaatactatt catggaaatg tttttcgatt acaataaaaa tagtatcaac 166620 aatcaactaa tgtatgatat aattaatagc gtatctataa ttctagctaa tgagagatat 166680 agaagcgctt ttaacgacga tggtatatac atccgtagaa atatgattaa caagttgtac 166740 ggatacgcat ctctaactac tattggcacg atcgctggag gtgtttgtta ttatctgttg 166800 atgcatctag ttagtttgta taaataatta tttcaatata ctagttaaaa ttttaagatt 166860 ttaaatgtat aaaaaactaa taacgttttt atttgtaata ggtgcattag catcctattc 166920 gaataatgag tacactccgt ttaataaact gagtgtaaaa ctctatatag atggagtaga 166980 taatatagaa aattcatata ctgatgataa taatgaattg gtgttaaatt ttaaagagta 167040 cacaatttct attattacag agtcatgcga cgtcggattt gattccatag atatagatgt 167100 tataaacgac tataaaatta ttgatatgta taccattgac tcgtctacta ttcaacgcag 167160 aggtcacacg tgtagaatat ctaccaaatt atcatgccat tatgataagt acccttatat 167220 tcacaaatat gatggtgatg agcaacaata ttctattact gcagagggaa aatgctataa 167280 aggaataaaa tatgaaataa gtatgatcaa cgatgatact ctattgagaa aacatatactct 167340 taaaattgga tctacttata tatttgatcg tcatggacat agtaatacat attattcaaa 167400 atatgatttt taaaaattta aaatatatta tcacttcagt gacagtagtc aaataacaaa 167460 caacaccatg agatatatta taattctcgc agttttgttc attaatagta tacacgctaa 167520 aataactagt tataagtttg aatccgtcaa ttttgattcc aaaattgaat ggactgggga 167580 tggtctatac aatatatccc ttaaaaatta tggcatcaag acgtggcaaa caatgtatac 167640 aaatgtacca gaaggaacat acgacatatc cgcatttcca aagaatgatt tcgtatcttt 167700 ctgggttaaa tttgaacaag gcgattataa agtggaagag tattgtacgg gactatgcgt 167760 cgaagtaaaa attggaccac cgactgtaac attgactgaa tacgacgacc atatcaattt 167820 gtacatcgag catccgtatg ctactagagg tagcaaaaag attcctattt acaaacgcgg 167880 tgacatgtgt gatatctact tgttgtatac ggctaacttc acattcggag attctaaaga 167940 accagtacca tatgatatcg atgactacga ttgcacgtct acaggttgca gcatagactt 168000 tgtcacaaca gaaaaagtgt gcgtgacagc acagggagcc acagaagggt ttctcgaaaa 168060 aattactcca tggagttcga aagtatgtct gacacctaaa aagagtgtat atacatgcgc 168120 aattagatcc aaagaagatg ttcccaattt caaggacaaa atggccagag ttatcaagag 168180 aaaatttaat aaacagtctc aatcttattt aactaaattt ctcggtagca catcaaatga 168240 tgttaccact tttcttagca tgcttaactt gactaaatat tcataactaa tttttattaa 168300 tgatacaaaa acgaaataaa actgcatatt atacactggt taacgccctt ataggctcta 168360 accattttca agatgaggtc cctgattata gtccttctgt tcccctctat catctactcc 168420 atgtctatta gacgatgtga gaagactgaa gaggaaacat ggggattgaa aatagggttg 168480 tgtataattg ccaaagattt ctatcccgaa agaactgatt gcagtgttca tctcccaact 168540 gcaagtgaag gattgataac tgaaggcaat ggattcaggg atatacgaaa caccgataaa 168600 ttataaaaaa agcaatgtgt ccgctgtttc cgttaataat actattttcg taactggcgg 168660 attattcata aataactcta atagcacgat cgtggttaac aatatggaaa aacttgacat 168720 ttataaagac aaacaatggt cgattataga aatgcctatg gctagggtat atcacggcat 168780 cgactcgaca tttggaatgt tatattttgc cggaggtcta tccgttaccg aacaatatgg 168840 taatttagag aaaaacaacg agatatcttg ttacaatcct agaacgaata agtggtttga 168900 tatttcatat actatttata agatatccat atcatcattg tgtaaactaa ataacgtctt 168960 ctatgtattt agtaaggaca ttggatatgt ggaaaagtat gatggtgcat ggaagttagt 169020 acatgatcgt ctccccgcta taaaggcatt atcaacttct ccttattgat tgaaaatgaa 169080 aatataaata gtttttatgt atagcagtat taccctatag ttttattgct tactactaac 169140 atggatacag atgttacaaa tgtagaagat atcataaatg aaatagatag agagaaagaa 169200 gaaatactaa aaaatgtaga aattgaaaat aataaaaaca ttaacaagaa tcatccaagt 169260 ggatattatta gagaagcact cgttattaat acaagtagta atagtgattc cattgataaa 169320 gaagttatag aatgtatcag tcacgatgta ggaatataga tcatatctac taatttttat 169380 aatcgataca aaacataaaa aacaactcgt tattacatag caggcatgga atccttcaag 169440 tattgttttg ataacgatgg caagaaatgg attatcggaa atactttata ttctggtaat 169500 tcaatactat ataaggtcag aaaaaatttc actagttcgt tctacaatta cgtaatgaaa 169560 atagatcaca aatcacacaa gccattgttg tctgaaatac gattctatat atctgtattg 169620 gatcctttga ctatcgacaa ctggacacgg gaacgtggta taaagtattt ggctattcca 169680 gatctgtatg gaattggaga aaccgatgat tatatgttct tcgttataaa gaattcggga 169740 agagtattcg ccccaaagga tactgaatca gtcttcgaag catgcgtcac tatgataaac 169800 acgttagagt ttatacactc tcgaggattt acccatggaa aaatagaacc gaggaatata 169860 ctgattagaa ataaacgtct ttcactaatt gactattcta gaactaacaa actatacaag 169920 agtggaaact cacatataga ttacaacgag gacatgataa cttcaggaaa tatcaattat 169980 atgtggtgtag acaatcatct tggagcaaca gtttcaaaac gaggagattt agaaatgttg 170040 ggatattgca tgatagaatg gttcggtggc aaacttccat ggaaaaacga aagtagtata 170100 aaagtaataa aacaaaaaaa agaatataaa aaatttatag ctactttctt tgaggactgt 170160 tttcctgaag gaaatgaacc tctggaatta gttagatata tagaattagt atacacgtta 170220 gattattctc aaactcctaa ttatgacaga ctacgtaaac tgtttataca agattgaaat 170280 tatattcttt ttttatagag tgtggtagtg ttacggatat ctaatattaa tattagacta 170340 tctctatcgc gctacacgac caatatcgat tactatggat atcttcaggg aaatcgcatc 170400 ttctatgaaa ggagagaatg tattcatttc tccagcgtca atctcgtcag tattgacaat 170460 actgtattat ggagctaatg gatccactgc tgaacagcta tcaaaatatg tagaaacgga 170520 ggagaacacg gataaggtta gcgctcagaa tatctcattc aaatccatga ataaagtata 170580 tgggcgatat tctgccgtgt ttaaagattc ctttttgaga aaaattggcg ataagtttca 170640 aactgttgac ttcactgatt gtcgcactat agatgcaatc aacaagtgtg tagatatctt 170700 tactgagggg aaaatcaatc cactattgga tgaaccattg tctcctgata cctgtctcct 170760 agcaattagt gccgtatact ttaaagcaaa atggttgatg ccattcgaaa aggaatttac 170820 cagtgattat cccttttacg tatctccgac ggaaatggta gatgtaagta tgatgtctat 170880 gtacggcaag gcatttaatc acgcatctgt aaaggaatca ttcggcaact tttcaatcat 170940 agaactgcca tatgttggag atactagtat gatggtcatt cttccagaca agattgatgg 171000 attagaatcc atagaacaaa atctaacaga tacaaatttt aagaaatggt gtaactctct 171060 ggaagctacg tttatcgatg ttcacattcc caagtttaag gtaacaggtt cgtataatct 171120 tgtggatact ctagtaaagt caggactgac agaggtgttc ggttcaactg gagattatag 171180 caatatgtgt aattcagatg tgagtgtcga cgctatgatt cacaaaacgt atatagatgt 171240 caatgaagag tatacagaag cagctgcagc aacttgtgca ctggtgtcag actgtgcatc 171300 aacaattaca aatgagttct gtgtagatca tccgttcatc tatgtgatta ggcatgttga 171360 tggaaaaatt cttttcgttg gtagatattg ctctccgaca actaattgtt aaccattttt 171420 tttaaaaaaa tagaaaaaac atgtggtatt agtgcaggtc gttgttcttc caattgcaat 171480 tggtaagatg acggccaact ttagtaccca cgtcttttca ccacagcact gtggatgtga 171540 cagactgacc agtattgatg acgtcagaca atgtttgact gaatatattt attggtcgtc 171600 ctatgcatac cgcaacaggc aatgcgctgg acagttgtat tccacactcc tctcttttag 171660 agatgatgcg gaatcagtgt tcatcgacat tcgcgagctg gtaaaaaata tgccgtggga 171720 tgatgtcaaa gattgtacag aaatcatccg ttgttatata ccggatgagc aaaaaaccat 171780 cagagagatt tcggccatca tcggactttg tgcatatgct gctacttact ggggaggtga 171840 agaccatccc actagtaaca gtctgaacgc attgtttgtg atgcttgaga tgctcaatta 171900 cgtggattat aacatcatat tccggcgtat gaattgatga gttgtacatc ttgacatttt 171960 ctttcttctc ttctcccttt cttctcttct cccttcctcc ctcttctccc tttcccagaa 172020 acaaactttt ttacccacta taaaataaaa tgagtatact acctattata tttcttccta 172080 tattttttta ttcttcattc gttcagactt ttaacgcgcc tgaatgtatc gacaaagggc 172140 aatattttgc atcattcatg gagttagaaa acgagccagt aatcttacca tgtcctcaaa 172200 taaatacgct atcatccgga tataatatat tagatatttt atgggaaaaa cgaggagcgg 172260 ataatgatag aattataccg atagataatg gtagcaatat gctaattctg aacccgacac 172320 aatcagactc tggtatttat atatgcatta ccacgaacga aacctactgt gacatgatgt 172380 cgttaaattt gacaatcgtg tctgtctcag aatcaaatat agatcttatc tcgtatccac 172440 aaatagtaaa tgagagatct actggcgaaa tggtatgtcc caatattaat gcatttattg 172500 ctagtaacgt aaacgcagat attatatgga gcggacatcg acgccttaga aataagagac 172560 ttaaacaacg gacacctgga attattacca tagaagatgt tagaaaaaat gatgctggtt 172620 attatacatg tgttttagaa tatatataca gaggtaaaac atataacgta accagaattg 172680 taaaattaga ggtacgggat aaaataatac cttctactat gcaattacca gatggcattg 172740 taacttcaat aggtagtaat ttgactattg cgtgtagagt atcgttgaga cctcccacaa 172800 cggatgcaga cgtcttttgg ataagtaatg gtatgtatta cgaagaagat gatggggacg 172860 gagacggtag aataagtgta gcaaataaaa tctatatgac cgataagaga cgtgttatta 172920 catcccggtt aaacattaat cctgtcaagg aagaagatgc tacaacgttt acgtgtatgg 172980 cgtttactat tcctagcatc agcaaaacag ttactgttag tataacgtga atgtatgttg 173040 ttacatttcc atgtcaattg agtttataag aatttttata cattatcttc caacaaacaa 173100 ttgacgaacg tattgctatg attaactccc acgatactat gcatattatt aatcattaac 173160 ttgcagacta tacctagtgc tattttgaca tactcatgtt cttgtgtaat tgcggtatct 173220 atattattaa agtacgtaaa tctagctata gttttattat ttaattttag ataatatacc 173280 gtctccttat ttttaaaaat tgccacatcc tttattaaat catgaatggg aatttctatg 173340 tcatcgttag tatattgtga acaacaagag cagatatcta taggaaaggg tggaatgcga 173400 tacattgatc tatgtagttt taaaacacac gcgaactttg aagaatttat ataaatcatt 173460 ccatcgatac atccttctat gttgacatgt atatatccag gaattctttt attaatgtca 173520 ggaaatgtat aaactaaaac attgcccgaa agcggtgcct ctatctgcgt tatatccgtt 173580 cttaacttac aaaatgtaac caataccttt gcatgacttg ttttgttcgg caacgttagt 173640 ttaaacttga cgaatggatt aattacaata gcatgatccg cgcatctatt aagttttttt 173700 actttaacgc ccttgtatgt ttttacagag actttatcta aatttctagt acttgtatgt 173760 gttataaata taacgggata tagaactgaa tcacctacct tagataccca attacatttt 173820 atcagatcca gataataaac aaattttgtc gccctaacta attctatatt gttatatatt 173880 ttacaattgg ttatgatatc atgtaataac ttggagtcta acgcgcatcg tcgtacgttt 173940 atacaattgt gatttagtgt agtatatcta cacatgtatt tttccgcact atagtattct 174000 ggactagtga taaaactatc gttatatctg tcttcaatga actcatcgag atattgctct 174060 ctgtcatatt catacacctg cataaacttt ctagacatct tacaatccgt gttattttag 174120 gatcatattt acatatttac gggtatatca aagatgttag attagttaat gggaatcgtc 174180 tataataatg aatattaaac aattatatga ggacttttac cacaaagcat cataaaaatg 174240 agtcgtcgtc tgatttatgt tttaaatatc aaccgcaaat caactcataa aatacaagag 174300 aatgaaatat atacatattt tagtcattgc aatatagacc atacttctac agaacttgat 174360 tttgtagtta aaaactatga tctaaacaga cgacaacatg taactgggta tactgcacta 174420 cactgctatt tgtataataa ttactttaca aacgatgtac tgaagatatt attaaatcat 174480 gacgtaaatg taacgatgaa aaccagtagc ggacgtatgc ctgtttatat attgcttact 174540 agatgttgca atatttcaca tgatgtagtg atagatatga tagacaaaga taaaaaccac 174600 ttattacata gagactattc caacctatta ctagagtata taaaatctcg ttacatgtta 174660 ttaaaggaag aggatatcga tgagaacata gtatccactt tattagataa gggaatcgat 174720 cctaacttta aacaagacgg atatacagcg ttacattatt attatttgtg tctcgcacac 174780 gtttataaac caggtgagtg tagaaaaccg ataacgataa aaaaggccaa gcgaattatt 174840 tctttgttta tacaacatgg agctaatcta aacgcgttag ataattgtgg taatacacca 174900 ttccatttgt atcttagtat tgaaatgtgt aataatattc atatgactaa aatgctgttg 174960 acttttaatc cgaatttcaa aatatgtaat aatcatggat taacgcctat actatgttat 175020 ataacttccg actacataca acacgatatt cttgttatgt taatacatca ctatgaaaca 175080 aatgttggag aaatgccgat agatgagcgt cgtatgatcg tattcgagtt tatcaaaaca 175140 tattctacac gtccggcaga ttcgataact tatttgatga ataggtttaa aaatataaat 175200 atttataccc gctatgaagg aaagacatta ttacacgtag catgtgaata taataataca 175260 cacgtaatag attatcttat acgtatcaac ggagatataa atgcgttaac cgacaataac 175320 aaacacgcta cacaactcat tatagataac aaagaaaatt ccccgtatac catcgattgt 175380 ttactgtata tacttagata tattgtagat aagaatgtga taagatcgtt ggtggatcaa 175440 cttccatctc tacctatctt cgatataaaa tcatttgaga aattcatatc ctactgtata 175500 cttttagatg acacatttta cgataggcac gttaagaatc gcgattctaa aacgtatcga 175560 tacgcatttt caaaatacat gtcgtttgat aaatacgatg gtataataac taaatgtcac 175620 gacgaaacaa tgttactcaa actgtccact gttctagaca ctacactata tgcagtttta 175680 agatgccata attcgaaaaa gttaagaaga tacctcaacg agttaaaaaa atataataac 175740 gataagtcct ttaaaatata ttctaatatt atgaatgaga gataccttaa tgtatattat 175800 aaagatatgt acgtgtcaaa ggtatatgat aaactatttc ctgttttcac agataaaaat 175860 tgtctactaa cattactacc ttcagaaatt atatacgaaa tattatacat gctgacaatt 175920 aacgatcttt ataatattc gtatccacct accaaagtat agttgtattt ttctcatgcg 175980 atgtgtgtaa aaaaactgat attatataaa tattttagtg ccgtataata aagatgacga 176040 tgaaaatgat ggtacatata tatttcgtat cattattgtt attgctattc cacagttacg 176100 ccatagacat cgaaaatgaa atcacagaat tcttcaataa aatgagagat actctaccag 176160 ctaaagactc taaatggttg aatccagcat gtatgttcgg aggcacaatg aatgatatag 176220 ccgctctagg agagccattc agcgcaaagt gtcctcctat tgaagacagt cttttatcgc 176280 acagatataa agactatggg gttaaatggg agaggctaga aaagaataga cggcgacagg 176340 tttctaataa acgtgttaaa catggtgatt tatggatagc caactataca tctaaattca 176400 gtaaccgtag gtatttgtgt accgtaacta caaagaatgg tgactgtgtt cagggtatag 176460 ttagatctca tattaaaaaa cctccttcat gcattccaaa aacatatgaa ctaggtactc 176520 atgataagta tggcatagac ttatactgtg gaattcttta cgcaaaacat tataataata 176580 taacttggta taaagataat aaggaaatta atatcgacga cattaagtat tcacaaacgg 176640 gaaagaaatt aattattcat aatccagagt tagaagatag tggaagatac aactgttacg 176700 ttcattacga cgacgttaga atcaagaatg atatcgtagt atcaagatgt aaaatactta 176760 cggttatacc gtcgcaagac cacaggttta aactaatact agatccaaaa atcaacgtaa 176820 cgataggaga acctgccaat ataacatgca ctgctgtgtc aacgtcatta ttgattgacg 176880 atgtactgat tgaatgggaa aatccatccg gatggcttat aggattcgat tttgatgtat 176940 actctgtttt aactagtaga ggcggtatta ccgaggcgac cttgtacttt gaaaatgtta 177000 ctgaagaata tataggtaat acatataaat gtcgtggaca caactattat tttgaaaaaa 177060 cccttacaac tacagtagta ttggagtaaa tacacaatgc atttttatat acattactga 177120 ataattatta ttattattta tatcgtattt gtgctataac gcgactatct aggtatttgt 177180 atctcactga tagagaacat ataaatatag actctattaa acagttgtgt aaaatatcaa 177240 atcctaatag atgtggatgt acggctttac atgagtactt ttataattat agatcagtca 177300 acggaaaata caagtataga tacaacggtt actatcaata ttatttatct agcgattatg 177360 aaaattataa tgaatattat tatgatgatt atgatagaac tggtatgaac agtgagaggtg 177420 ataatatatc aatcaaaaca gaatatgaat tctatgatga aacacaagat caaagtacac 177480 aactagtagg ttacgacatt aaactcaaaa ccaatgagga tgattttatg gctatgatag 177540 atcagtgggt gtccatgatt atatagatga atcaattaat aaagtagtat atggaagaga 177600 gtctcacgta agatggcggg atatatggca agaacataat gatggcgtat acagtatagg 177660 aaaggagtgc atagataata tatacgaaga caaccatacc gtagacgaat tctacaagat 177720 agacagcgta tcagatgtag atgacgcgga acacatatct ccgataacta atgatgtatc 177780 tacacaaaca tgggaaaaga aatcagagtt agatagatac atggaaatgt atcctcgtca 177840 tagatatagt aagcattctg tctttaaggg attttctgac aaagttagaa aaaatgattt 177900 agacatgaat gtggtaaaag aattactttc taacggtgca tctctaacaa ttaaggatag 177960 cagtaataag gatccaataa ccgtttattt tcgaagaacg ataatgaatt tagaaatgat 178020 tgatattatt aacaaacata caactattga tgaacgaaag tatatagtac actcctatct 178080 aaaaaattat aaaaatttcg attatccatt tttcaggaag ttagttttga ctaataaaca 178140 ttgtctcaac aattattata atataagcga cagcaaatat ggaacaccgc tacatatatt 178200 ggcgtctaat aaaaaattaa taactcctaa ttacatgaag ttattagtgt ataacggaaa 178260 tgatataaac gcacgaggtg aagatacaca aatgcgaact ccattacaca aatatttgtg 178320 taaatttgta tatcataata ttgaatatgg tatccgatac tataatgaaa agattataga 178380 cgcatttata gagttaggag ccgatctaac tattccaaat aacgatggaa tgataccagt 178440 agtttactgt atacactcaa atgcagaata tggttataac aatattacta acataaagat 178500 aatacgtaaa ctacttaatc ttagtagacg tgcgtcacat aatctattta gagatcgagt 178560 catgcacgat tatataagta atacatatat tgatcttgag tgtttagata ttattagatc 178620 gttggatgga ttcgatatca atggttactt tgaaggacgt acaccacttc attgcgctat 178680 acaacataac ttcactcaga ttgctaagta cttattagat cgaggagctg atatagtcgt 178740 acccaacaca ttgattatac atcagtacat acagtaaata gcatagatat ggaggaggat 178800 acaaatattt caaataaagt tataaggtac aacactgtca ataatatatg gaagacatta 178860 cctaacttct ggactggaac tataaatcca ggcgtggtct cgcataaaga tgatatatat 178920 gttgtatgcg acatcaaaga tgaaaaaaat gttaagactt gtatatttag atataacacg 178980 aatacgtata acggatggga attggttacg acgacagaaa gcagattatc agctctgcat 179040 actattcttc atgacaatac cataatgatg ttacattgtt atgaatcgta tatgttacaa 179100 gatacattta atgtgtacac tcgcgaatgg aatcatatgt gtcatcaaca ttcgaatagt 179160 tatatcatgt acaatatact acccatctac taaatataat agaataaaat aaatgagtat 179220 gatcatttta gataacgatt gattttatca ttaccgcttc attcttatat tctttgctta 179280 cggaacctat atttagaaac atctactaac gattttttat gcttgcatta ttaatggtat 179340 gtaatatgat tgattgtgta cgcaatacca atttgttaag tatgaatacg gggtacaaac 179400 ataaactgaa atttaacatt atttatttat gatatatatc gttatcgtta ttgtttggtc 179460 tataccatgg atatctttaa agaactaatc ttaaaacacc ctgatgaaaa tgttttgatt 179520 tctccagttt ctattttatc tactttatct attctaaatc atggagcagc tggttctaca 179580 gctgaacaac tatcaaaata tatagagaat atgaatgaga atacacccga tgataagaag 179640 gatgacaata atgacatgga cgtagatatt ccgtattgtg cgacactagc taccgcaaat 179700 aaaatatacg gtagcgatag tatcgagttc cacgcctcct tcctacaaaa aataaaagac 179760 gattttcaaa ctgtaaactt taataatgct aaccaaacaa aggaactaat caacgaatgg 179820 gttaagacga tgacaaatgg taaaattaat tccttatga ctagtccgct atccattaat 179880 actcgtatga cagttgttag cgccgtccat tttaaagcaa tgtggaaata tccattttct 179940 aaacatctta catatacaga caagttttat atttctaaga atatagttac cagtgttgat 180000 atgatggtgg gtaccgagaa taacttgcaa tatgtacata ttaatgaatt attcggagga 180060 ttctctatta tcgatattcc atacgaggga aactctagta tggtaattat actaccggac 180120 gacatagaag gtatatataa catagaaaaa aatataacag atgaaaaatt taaaaaatgg 180180 tgtggtatgt tatctactaa aagtatagac ttgtatatgc caaagtttaa agtggaaatg 180240 acagaaccgt ataatctggt accgatttta gaaaatttag gacttactaa tatattcgga 180300 tattatgcag attttagcaa gatgtgtaat gaaactatca ctgtagaaaa atttctacat 180360 acgacgttta tagatgttaa tgaggagtat acagaagcat cggccgttac aggagtattt 180420 atgactaact tttcgatggt atatcgtacg aaggtctaca taaaccatcc attcatgtac 180480 atgattaaag acaacacagg acgtatactt tttataggga aatactgcta tccgcaataa 180540 atataaacaa atagactttt atcacgttta tctatgtcta aatattacaa atagtaatag 180600 tataaactaa agctgataat acttaaaaaa ataataatat catttacaat taatagtata 180660 aactaaaaat taaacaaatc gttattataa gtaatatcaa aatgatgata tacggattaa 180720 tagcgtgtct tatattcgtg acttcatcca tcgctagtcc actttatatt cccgttattc 180780 cacccattac ggaagataaa tcgttcaata gtgtagaggt attagtttcc ttgtttagag 180840 atgaccaaaa agactatacg gtaacttctc agttcaataa ctacactatc gataccaaag 180900 actggactat cggcgtacta tccacacctg atggtttgga tataccattg actaatataa 180960 cttattggtc acggtttaact ataggtcgtg cattgttcaa atcagagtct gaggatattt 181020 tccaaaagaa aatgagtatt ctaggtgttt ctatagaatg taagaagtcg tcgacattac 181080 ttactttttt gaccgtgcgt aaaatgactc gagtatttaa taaatttcca gatatggctt 181140 attatcgagg agactgttta aaagccgttt atgtaacaat gacttataaa aatactaaaa 181200 ctggagagac tgattacacg tacctctcta atggggggtt gcctgcatac tatcgtaatg 181260 gggtcgatgg ttgattattg attagtatat tccttattca cacaaaaaga acatttttat 181320 aaacatgaaa ccactgtcta aatgtaatta tgatcttgat ttatagatga agatcagcct 181380 ttagaggatt ttaaccagta tgtttaatat gaaaaaaata aacataacat attttgagat 181440 taagcgctat tgtgcttaat tattttgctc tataaactga atatatagcc acaattattg 181500 acgggcttgt ttatgaccgg caatcatgaa tttacagaaa ttatctctgg ctatatct 181560 tactgcgaca tgttcgtggt gttatgaaac atgcataaga aaaactgcgt tgtatcatga 181620 cattcaattg gagcatgtag aagacaataa agatagtgta gcgtcgctac cgtacaagta 181680 gtcaatcaaa gagaacgtag tagattgttg gctacattta attggacaga tatagctgag 181740 ggtgttagaa atgagttcat taaaatatgt gatatcaacg gaacatattt atataattat 181800 actattgctg ttagtataat tattgattcc acggaagaac taccaacagt tactccaatt 181860 acaacaacat atgaaccttc tacatataat tatactatcg atgatagcac tgttattact 181920 actgaagaac tacaagtgac tcctcatatg gatctccatc gatgatacat gtattaaaat 181980 actttccgaa taagtctttt aaatattgta ttaattatga aaaactatgc tatgcgagta 182040 tgatgcaaag atgtttaatg atacgatact agattttatc tctagcgaga gatgtcgtta 182100 gaatcattta tcataactac gtttaataat aattcatcaa cgaatatcga taacatgtgt 182160 catttatacg ttaaagtctg tccgtcttct ctattgttta gactgtttgt agaatgctgt 182220 gatataaaca aactagtaga aggtacgact ccgttacact gttatctaat gaatgaagga 182280 tttgaatcat ctgttttaaa aaacctatta aaggagtatg tcatgaatac gtttaatgtt 182340 catgacatcc attacacaaa tatttaactc atgatgaagt tgagaatgat atgctttctg 182400 atatataga tagctttagc taatataaaa atatattaat ccactatata ttctagactt 182460 gatttaaaac cgataaacta ctactacgta ctgtataagt tgttaaaaaa aggagcagac 182520 cctaattatg tagatgatag aggtaatact tttcttcatt acttctgcat ctatatgtcc 182580 acttatgaga aaacgtcatt taataagatg catcgtgaaa agaaatttat taaagagttg 182640 gtaaaatatg aaaccgaaag taaataatat aggaaataca cctctacata actacgtatc 182700 tcaatatgat atcactctca ttcctcatcc acaacccatt aaaaaaatgg aaattaaagc 182760 cctctattag cataaacggc tacaggtcta cctttacaat ggcctctcct tgtgcccagt 182820 tcagaccctg tcattgccac gctactaagg actccctgaa taccgtggcc gacgtcagac 182880 attgtctgac tgaatacatc ctgtgggttt ctcatagatg gacccataga gaaagcgcag 182940 ggtctctcta caggcttctc atctctttca gaactgatgc aacggagctc tttggtggtg 183000 agttgaagga ttcacttccg tgggacaata tcgacaattg cgtggagatc attaaatgtt 183060 tcatcagaaa tgactccatg aaaaccgccg aagaacttcg tgcaatcatt ggactttgta 183120 ctcaatcagc tatcgtctct ggaagagtct tcaacgataa gtatatcgac atactactta 183180 tgctgcgaaa gattctgaac gagaacgact atctcaccct cttggatcat atccgcactg 183240 ctaaatacta aatctccttc atgctctctc actacacttt ttatcatctt atgaggaatg 183300 attgccttca tcatttttcg tgaaatagga ataattagca ccagaatagc tatggattgc 183360 acatgtattc tatgtcgtct actggatgaa gatgtgacgt acaaaaaaat aaaactagaa 183420 attgaaacgt gtcacaactt atcaaaacat atagatagac gaggaaacaa tgcgctacat 183480 tgttacgtct tcaataaatg cgatacagac attaagattg ttcgactgtt actctctcgc 183540 ggagtcgaga gactttgtag aaacaacgaa ggattaactc cgctaggagc atacagtaag 183600 catagatacg taaaatctca aattgtgcat ctactgatat ccagctattc gaattcctct 183660 aacgaactca agtcgaatat aaatgatttc gatctgtatt cgtatatgtc ttcggataat 183720 atcgacttac gtctgctaaa atacctaatt gtggataaac ggatacgtcc gtccaagaat 183780 acgaattatg caatcaatgg tctcggattg gtggatatat acgtaacgac gcctaatccg 183840 agaccagaag tattgctatg gcttcttaaa tcagaatgtt acagcaccgg ttacgtattt 183900 cgtacctgta tgtacgacag tgatatgtgt aagaactctc ttcattacta tatatcgtct 183960 catagagaat ctcaatctct atccaaggat gtaattaaat gtttgatcaa taacaatgtt 184020 tccatccatg gcagagacga aggaggatct ttacccatcc aatactactg gtcttgctca 184080 accatagata tagagattgt taaattatta ataaaggatg tggacacgtg tagagtatac 184140 gacgtcagcc ctatattaga ggcggattat ctaaacaagc gatttagagt aaccccatat 184200 aatgtagaca tggaaatcgt taatcttctt attgagagac gtcatactct tgtcgacgta 184260 atgcgtagta ttacttctta cgattccaga gactataacc actacatcat cgataacatt 184320 ctaaagagat ttagacaaca ggatgaatcc atcgtacaag ccatgttgat aaactactta 184380 cattacggcg atatggtcgt tcgatgcatg ttagataacg gacaacaact atcctctgca 184440 cgactacttt gttaataata atctcgtcga tgtaaacgtc gtaaggttta tcgtgggaaaa 184500 taatggacac atggctgtaa atcacgtatc gaacaatggc cgtctatgta tgtacggtct 184560 gatattatcg agatttaata attgcgggta tcactgttat gaaaccatac taatagatgt 184620 atttgatata ctaagcaagt acatggataa tatagatatg atcgataatg agaataaaac 184680 tctactatat tacgcggtcg atgtcaataa tatacaattt gcaaagcggt tattggaata 184740 tggagcgagt gttacaacat cacgctcgat aatcaatacg gccatccaga aaagtagtta 184800 cagaagagaa aacaaaacga ggatagttga tttattactt agctaccatc ccactctaga 184860 gactatgatt gacgcattta atagagatat acgctatcta tatcctgaac cattattcgc 184920 ctgtatcaga tacgccttaa tcctagatga tgattttcct tctaaagtaa gtatgatatc 184980 tccggtcgtc ataaggaact aaagcgctat agagtagaca ttaatagaat gaagaatgcc 185040 tacatatcag gcgtctccat gtttgatata ttatttaaac gaagcaaacg ccacagattg 185100 agatacgcaa agaatccgac atcaaatggt acaaaaaaga actaacgtcc atcattacag 185160 aaactgtaaa gaacaatgag aggatcgact ccatagtgga caacattaat acagacgata 185220 acttgatttc gaaattaccc atggagatac tttattactc cattaaataa tttatcatgg 185280 agcgataatg tcctgtttca tttgtttcca tgacatatta caaaatcgat tccgtccaag 185340 atgataaaaa catttaccgg catcataaac acggagttta ttttatatgt ctcgcataaa 185400 cattactaaa aaaatatatt gttctgtttt tctttcacat ctttaattat gaaaaagtaa 185460 atcattatga gatggacgag attgtacgca tcgttcgcga cagtatgtgg tacataccta 185520 acgtattat ggacgacggt aagaatgaag gtcacgtttc tgtcaacaat gtttgtcata 185580 tgtattttac gttctttgat gtggatacat cgtctcatct gtttaagcta gttattaaac 185640 actgcgatct gaataaacga ggtaactctc cattacattg ctatacgatg aatacacgat 185700 ttaatccatc tgtattaaag atattgttac accacggcat gcgtaacttt gatagcaagg 185760 atgaaaaagg acatattcct ctacaccact atctgattca ttcactatca atcgataaca 185820 agatctttga tatactaacg gacaccattg atgactttag taaatcatcc gatctattgc 185880 tgtgttatct tagatataaa ttcaatggga gcttaaacta ttacgttctg tacaaaggat 185940 ccgaccctaa ttgcgtcgac gaggatggac tcacttctct tcattactac tgtaaacaca 186000 tatccacgtt ctacaaaagc aattattaca agttaagtca cactaagatg cgagccgaga 186060 agcgattcat ctacgcgata atagattatg gagcaaacat taacgcggtt acacacttac 186120 cttcaacagt ataccaaaca tagtcctcgt gtggtgtatg ctcttttatc tcgaggagcc 186180 gatacgagga tacgtaataa tcttgattgt acacccatca tggaacgatt gtgcaacagg 186240 tcatattctc ataatgttac tcaattggca cgaacaaaag gaagaaggac aacatctact 186300 ttatctattc ataaacata atcaaggata cactctcaat atactacggt atctactaga 186360 taggttcgac attcagaaag acgaatacta taataccgcc tttcaaaatt gtaacaacaa 186420 tgttgcctca tacatcggat acgacatcaa ccttccgact aaagacggta ttcgacttgg 186480 tgtttgaaaa cagaaacatc atatacaagg cggatgttgt gaatgacatc atccaccaca 186540 gactgaaagt atctctacct atgattaaat cgttgttcta caagatgtct ctccctacga 186600 cgattactac gtaaaaaaga tactagccta ctgcctatta agggacgagt cattcgcgga 186660 actacatagt aaattctgtt taaacgagga ctataaaagt gtatttatga aaaatatatc 186720 attcgataag atagattcca tcatcgtgac ataagtcgcc ttaaagagat tcgaatctcc 186780 gacaccgacc tgtatacggt atcacagcta tcttaaagcc atacattcag acagtcacat 186840 ttcatttccc atgtacgacg atctcaaacc cgtacccaga aataccttta actatatcga 186900 tgtggaaatt aatctgtatc ccgtcaacga cacatcgtgt actcggacga ccactaccgg 186960 tctcagcgaa tccatctcaa cgtcggaact aactattact atgaatcata aagactgtaa 187020 tcccgtcttt cgtgatggat acttctccgt tcttaataag gtagcaactt caggattctt 187080 tacaggagaa aggtgtgcac tctgaatttc gagattaaat gcaataacaa agattcttcc 187140 tccaaacagt taacgaaagc aaagaatgat actatcatgc cgcattcgga gacagtaact 187200 ctagcgtcga catctatata ctatatagta ataccaatac tcaagactac gaaactgata 187260 caatctctta tcatgtgggt aatgtagcca tatgcccggt agttgcgata tacataaact 187320 gatcactaat tccaaaccca cccgcttttt atagtaagtt tttcacccat aaatacaata 187380 attaatttct cgtaaaagta gaaaatatat tctaatttat tgcacggtaa ggaagtagaa 187440 tcataaagaa cagtactcaa tcaatagcaa tcatgaaaca atatatcgta ctggcatgca 187500 tgtgcctgcc agtcttcagc aatcatcctc atcgtgtacg gaagaagaaa acaaaca 187560 tatgggaatc gatgttatta tcaaagtcac aaagcaagac caaacaccga ccgatgataa 187620 gatttgccaa tccgtaacgg aaattacaga gtccgagtca gatccagatc ccgaggtgga 187680 atcagtcgag gatgtagatc ctcctaccac ttattactcc atcatcggtg gaggtctgag 187740 aatgaacttt ggattcacca aatgtcctca gattaaatcc atctcagaat ccgctgatgg 187800 aaagactgtg aggtgtctat cgacatcaga tgtagcgaag aagagaaaga cagcgacatc 187860 aagacccatc cagtactcgg gtctaacatc tctcataaga aagtgagtta cgaagatatc 187920 atcggttcaa cgatcgtcga tacaaaatgt gtcaagaatc tagagtttag cgttcgtatc 187980 ggagacatgt gcaaggaatc atctgaactt gaggtcaagt atgtcgacgg atcggcatct 188040 gaaggtgcaa ccgatgatac ttcactcatc gattcaacaa aactcaaagc gtgtgtctga 188100 atcgataact ctattcatct gaaattggat gagtagggtt aatcgaacga ttcaggcaca 188160 ccacgaatta aaaaagtgta ccggacacta tattccggtt tgcaaaacaa aaagttacct 188220 ctcgcgactt cttctttttc tgtctcaata gtgtgatacg attatgacac tattcctatt 188280 cctatttcct ttcagggtat cacaaaaata ttaaacctct ttctgatggt ctcataaaaa 188340 aagttttaca aaaatatttt tttatctct ttctctcttt gatggtctca taaaaaaagt 188400 tttacaaaaa tatttttatt ctctttctct ctttgatggt ctcataaaaa aagttttaca 188460 aaaatatttt tattctcttt ctctctttga tggtctcata aaaaaagttt tacaaaaata 188520 ttttattct ctttctctct ttgatggtct cataaaaaaa gttttacaaa aatattttta 188580 ttctctttct ctctttgatg gtctcataaa aaaagtttta caaaaatatt tttatctct 188640 ttctctcttt gatggtctca taaaaaatat taaacctctt tctgatggtg tcactaaaat 188700 attttattc tcattctcat tttctctttc tctcttcaat ggagtcataa aatattttta 188760 ttctctttct ctcttcgatg gtctcacaaa aatattaaac ctctttctga tggtgtcact 188820 aaaatatttt tattctcatt ctcattttct ctttctctct tcaatggagt cataaaatat 188880 tttattctc tttctctctt cgatggtctc acaaaaatat taaacctctt tctgatggag 188940 tcgtaaaaaa gttttatctc tttctctctt cgatggtctc actaaaatat tttttattct 189000 ctttctgatg catcaactat ttcttaaaca ataacgtcca acaacatata ctcgtcgagc 189060 ttatcaacat cccctatgcc catctaggtt accagacaat tgtatatcat aaaataatgt 189120 ttataattta cacgttaaaa tcatataata aaacgtagat cgtataatat tttttggtat 189180 ataaatgatc tagtaaaatc catgtaggggg atactgctca cattttttct ttggtacaaa 189240 atttcacaca agtttttata cagacaaatt cttgtccata tattttaaaa cattgacttt 189300 tgtactaaga aaaatatcta gactaactat ctctttctct ttctctcttc gatggtctca 189360 caaaaatatt aaacctcttt ctgatggagt cgtaaaaaag ttttatctct ttctc 189415 <210> 2 <211> 138203 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 2 ccggcgaagc cgcggatccg ctgttccggc gaaggcagga cagacatttt ttccagccca 60 taaattaaaa agaatcaaca gaaaattatc atgatgataa aaacttttag gattgtattt 120 agttgaacgt ttcgtcaata aatcaacctc aaattttttc acatgtaatt tcttgttctt 180 tttaattat gggctggaaa aaatgtctgt cctgccttcg ccggaacagc ggatccgcgg 240 cttcgccggg gcggcggccg gctcccgcgg cggctgagcc gcgctgccgc gagaacgcgg 300 accaggagtt cctgcgggag gagctacggc agaggctgga actgctgaat gctttcgagg 360 acgggcgtcc gcgggaacgc gactccgcgg aggcggcacc ccgcagccgc gagacctcgc 420 tctggagtca gggagtcagg gagtcggggag tcagggagtc gggagtcagg gagtcggggag 480 tcagggagtc gggagtcagg gagtcggggag tcagggagtc gggagtcagg gagtcggggag 540 tcagggagtc gggagtcagg gagtcggggag tcagggagtc gggagtcagg gagtcggggag 600 tcagggagtc gggagtcagg gagtcggggag tcagggagtc gggagtcagg gagtcggggag 660 tcagggagtc gggagtcagg gagtcggggag tcagggaaac agaagtcaag tagtcgggta 720 gacaggagtc aggtggtcgg gtgaccgcgc cgtccgagtc ccgcaaaaag tttttagact 780 ctgagagagg ccgacctgcc tccaacggtt ccgcggaaaa gtttttataa aaagttttcg 840 ggagaggccg actgccttcc aacggttcct cctctcgcgt gccgcgggcg gccgctctcc 900 cgcgacggtc ccgccaacgc gtttacaaag ttttaaaagt tttcgagaga ggccgacctg 960 tcttccaacg gttgcgcgaa aaggttctgc ggaggtttgg aagagccgcc cgccctccga 1020 catcctccga aaagttttcg caaaaagttt ttaaaggttt cgcgaggagt tttcgaggga 1080 ggcgacctgc ctccgaggtt ccgcgtaaac gtttttacaa agcgtcggag gtggggggcga 1140 cctgcccttc ctctcctccg aaaagctctt gagagtgtgg gagaggcggc cggccttcgc 1200 ggtcgcgcga aaaggttctg cgggagttcg cgggagctga cccgccctcc gcgcccctcc 1260 gaaaagtttt tgcacgaagt cttttggcgt tctcgagagg acgcctaccc cgacggtaac 1320 gcggaacgtc tcgggaggtc ggcctctccg ctcccgcggt cgcgggcggc ggcccgtctc 1380 cggaggttcc gcgaaaagtt ttataaaaag ttttgaggga ggtaccgacc tcctaaagtt 1440 ttacagagag ttctcgcaaa agttttggga ggtcgacctg acctcctaaa gttatcgaag 1500 agttctcgcg aagagttctc gcaaagagtt tgagaggccg acctgcctcc aacggttccg 1560 cggaaaagtt ttataagagt tttgagagag gtcgacctac cttccaacgg ttccgcggaa 1620 aagttttata agagttttga gagaggtcga cctactctcc gaggttccgc ggaaagtttt 1680 ataaaaagtt tttacaaagt ttttgaggga ggtcgacacc ctccggatcc tccgcctcgc 1740 gtgccgcggg cggcctccaa gagttttacg gaacgttctg gagaggagag gccgacctcc 1800 caaagatttt gcggaacgtt ttggagagga ggactggcct cgaaaagatt ttacaaagag 1860 tttggaggga ggactggcct ccaacggttc cgcgaaaaag ttttgcaaga gtttggagag 1920 aggtcgacca ccctccgagg ttccgcgaaa gtgtttgcgg agagtccgag agaggcagac 1980 actgcctgcg aaaagttttc gcggacggtt gagcgggtca ccgacctccg acagtttaca 2040 aacgttttac ggagagttag agaggcagca gaccgacctc cgaacagttt agttttacaa 2100 agttttggag ggtgaactgt catcgggaaa gttttacgaa gagttttggg agaggccgac 2160 ggttagccga gcgagcgcgc gagcgagttt acgttctctc gctcgtgtgc gcgttaactc 2220 gcactggttc cctctctaac tcggagtggg cgagcgagtg gttgactcgt cctccgctct 2280 cactctgagt ggtgataact gttaaccatt aactcgtcct ccactctctc actctctcac 2340 tctgagtgag gattgacttg ttaactcgtc ctccactctc tcgctctctc gctctgagtg 2400 agtgaggatt aactgttcaa ctcgtcaact cgtcctctgc ctctcatcca agactgagtg 2460 ggtagttgac tgctcttgtt ctcttactcc gaggggtgat tgagttagca acagctactc 2520 gttctcttgt tctctcacac cgagtgagcg agtgagcaac gttacttgtt ctctcacacc 2580 gagtgagcga gtgagcaacg gttaactcgt tctctcgttc tctcgttcta ttatattccgag 2640 gagtggcgag tgaggtaacg gttactgtta cttgttctct gttcccttcc tcggtgagcg 2700 gtgcgtcaac ttgttctcgt gagtgagtac ggtcacttgt tctctcgttc tctacctcga 2760 ggaggtgagtc aacttgttct cgtgagtgag ttgaccgtaa ccgttccctt acctcaagtg 2820 agtggcggtc gcttgttctc gtgagtgggt taaccgcgtt cccttaccgg agtgagcggg 2880 cgggcgataa aaataatcaa ttgactgatt cgctcgtgag cgagcgaagg gcggcggaca 2940 agggcgcggg atgctggtct aatctactaa ggccgattac aaaaacggat gggagaccgg 3000 gagggagagg gtcacagctc cgagcggtgc atccgcgcca gctggcggcg ccactcggcc 3060 gcgggccgcg cggccgccca ggccgcgttg tagccgcccg ccaccgcgac gcaggtcagc 3120 tcgaactccg gcccgagcgc gcgcacgtcg tagatgtgca cggtcgcgac gttcagcagc 3180 agcgcgccct tgcgcagcga ggcgaaggtc gcgtgcatgc cggcggcgag cgggtacacc 3240 ggcgagagcg tcccgccgcc gtgcgcgacc accgccatgt gccgcccgtc gccgccgacg 3300 gtcaggcagg tcaccgaggc ggagccgttc gcgcggacgg ggcccgcctc cacgagggcg 3360 gccggcagcg gcggcgccgc ggggcggaag agcccgccga ggaggaagcc cagcgccacc 3420 agcgcgagcg cgccgagcag cctgcgcggc gaggggtgca tgcttgttgg ctgcggtgtt 3480 ggcgtctggc gggtgggaagg cgggtgtggg gtgtccgcgg ctgcggcggg agggtctcga 3540 ctgctaggcg gtcctttttc actttgctcc gtggcgcctg gtccggggca agggctgcgg 3600 cgggcgcccg ggcgggcggg ccgctacccc gccgcgcggc ccgcggccgc cagcgccgcg 3660 gccagccgcc gccaccgcgg gcccgccgcg cgcagcagcc ccgccgccga gcgccccgcg 3720 ccgccgcggg cgcgcgccga ggccgcggcc ccgcgccgcg ccagcagcag cggcagccgc 3780 gcgtccagcg ggccgccgcg gcgcagcgcc gcgcgcagca gcgccgccag cggcagccgc 3840 cccgccgcgt ccgggcccgc cgcgcgcgcg cccgccgcca gcagcgcgcg caccagcgcc 3900 ggcgaggggc gccgcgcgcg gaccaggtgc tccacgagca gggtggtgag caaggattct 3960 cgagaagtag gagtcatgtg tgacgacaag gagagacgtt atattaggcg cgtcctactt 4020 cactttgaag atggtgtaaa gtgttaaaac ttgaacaccg ttcactccac cactgccgtt 4080 accgtgtcct gccccaaaag caaccacagt gctttttcca ccacctgttc caaatccgtt 4140 ccaaaagctc ccatccattg ttgttagaac tttcagatgt ttctctaggt tgtttagttc 4200 cactgcaagt ttcgaccatt atcgttactg gacatgctgt tggtaatgag tttaataacc 4260 aatcataaaa atagttataa tttgttataa agctaataaa gtagcaaaca ctttaatgtt 4320 atattttgcc taaccctccg ttaacaccac cattaacacc accacttaag cttttactac 4380 caccactacc acctccaaca cacattcttt tctctaaagg tccccaaatt ccacctcctg 4440 aacttggacg ttttacagca cctccgggtg tacttgcgta ccctttagaa gttccactgt 4500 gactgtagat atgatactgt ccttctccag gcatgattaa agtgtgttgt aattagtgtt 4560 atctacgcaa ctgtgcgaga ctctcgaata aaaagaagct acattttaca attttgatta 4620 gctgatgtac cacgctgtat cgcggccacc acaagcaccc gatccagtag aaccaaatcc 4680 agagtcgccg cggtcagtgt tgtccaagca gttaacctct tgaactgctg ggcacgatat 4740 gcgttcgcat attagctgag ctatcctgtc tcccttctta acctcaaagt cactgtttcc 4800 aaagttaaac agcaccactc cgacgttgcc tcggtagtct tcgtcgatca cgccagcgcc 4860 cacgtcgata aagtgtttga ctgcaaggcc agaacgtggt gctatgcgtc cgtagcaacc 4920 agaagggggc tttatcagaa ggtcagtaaa tactacgcga ctgcaatgcg aagggatgac 4980 acagtcgtat gcactacata ggtctaatcc tgcggcacca ggagatcctc tggctggtat 5040 agtggcgttt tggctgaggc gaacaacctg aagagtttcc gtgtggcaga actccatggc 5100 tagggtggcg agcggccgat cgactacggg gtgtacaatt tacactttct ccagaaaaat 5160 caggggcggg tcagcatggc gcggcgcaag tccagcagcg agtcgtacga caggaagcac 5220 aggatggagg tcacgatctc cggcggcagg gcgcacgggc acatgaggcc ggcgatctgc 5280 tcggccagcg agacgcgcag ccgcatcatg cagatcttgc cgaagagcgc cgtcccgtag 5340 atggggaact cggccgcgcg ctccaaaaag gcgttctgca cgaagagcgc cttcgcgtcg 5400 tccgacgcgc gcagcacgtc caacagcgtc gcgtccgtgt ggcagcgcac cgcgcgcatg 5460 cttgcgatct cctgctcgca cgcgcggatc acggtcgcgt agtccgccag cgcgcgctcc 5520 gccagcatgc gcgcgccctc gccgcgcagc gccagctcct gcacgcacag cagcgcggcc 5580 tccgagcgtc ggaacacgtg gccccattgc tcggatgtga tcagcgcgcg cgcgagcagc 5640 tccgtcggcg gccggcgcgc gagcacggcc gccgtcgcgc gcacgttgtt gcggcgcagc 5700 atctccgaaa ccgcgcatag gcccgaggcc gacatgtgct cgagctccgc gcccatgcgc 5760 accagccggc agcaggcgcc gtggctgaac accgccgcgc ggtgcagcgc ggtctgcagg 5820 ttgttgttgc gcaggttcag gtccagcccg cgctcgagca cgaagtccac gacgccgcgc 5880 tcgcagctcc cgtaggtcgc catgtagtgc agcatggtgt tcccacacgc gtctacggcg 5940 gccgggtcca cgcctaggcc cgtgagcgtg cgcaccatgc cctcggagat cttggccgtg 6000 cgcgcgaggt ggtgcagcgt tgtgcgcccg tacgcgtcca cgacgcacgc gtccgcgccc 6060 gcgcgcagca tcatgtccac gagcgcggcg gagacgccgc cggagcacag cagcgccgcc 6120 agcggcgtca agccgttgca gtcgcaggcg tttgggttcg cgccgcgctc gagcagcagc 6180 cgcagcacgt cctcgcggat ccactggttc ttggcgtaca cgtgcagcgg cgttacgccg 6240 taggtgttgc cctcgttcac gcgcgcgccc gcgtccagca gcagccgcgc gacctcgagc 6300 tcggcgccgt cggggccgca gaaagccagg aaggaggaga gcacgctgtc gcagacaacg 6360 acgctggcgt cgcagaccac gtccgcgccc gcctccagca tgagcgcgac cacctccggc 6420 cgcacgccgt cgtactgcac gtaggcgtgc agcggcgtgc ggccgcagga gtccttggct 6480 ttcacgtccg caccggcctc cagcagcacg cgcacgatct ccgcgcactg ctcgtgccgc 6540 gcgaagtgca cgcagaggtg cagcggcgtg cgcccgtgct cgccgcggaa gttcacgtct 6600 gcgtcggtgg ctacgagcgc gcggaccgtt tcgaggtcca cctgcccgga ctccaggtag 6660 cggaagagca ggtccgcgtg cgggaccacg acggactccc gcgagagcat ggcggcgttt 6720 acaaatattg aaatcttttt tcactcatct ttatgggcgc tgaacgcgca ataagggtga 6780 gagtaaaaaa cttctacaaa aagcgtacaa aaggtacaaa aggtaaaaaa ggcggggcgg 6840 ggacgggctg gggtgctgcg agctgaattg gcctctacac agggacgccc tcgccggagc 6900 cggtgagccg gtagccggcg ccggcgatca tggtcaagcg ctgcacgagc tcgttgcgct 6960 tgacgccggc ctctgaaacg cacaccatgt ggtggatgta ccgctcgatg cactcgcagc 7020 7080 acttgctgta cagttctcgg aggtctctct ccattcgagc cgtaagagag tcaggatgcg 7140 gtgttccttc gggagtctga gcgaacaccg cgaacaggct ggttatgccg tgttctagaa 7200 tagagtggtt ccgcgttaat gccgcagaca agggtcgtcg tccgcgcaac gactggcggc 7260 agagcgctgt ttgtgccgca ccgcccattc ctctggcgat cgcatccacc gacgcagtga 7320 tcatctgcgc gccgacgtca ttgtagcgcg cgttaaactc agtaatcatg attacgagat 7380 7440 tcttgcacgc ctttcgccgc gtctccgcca cgttggcgac tcggacttgc gcttcctggt 7500 cgatggacgg cggaaacact tcaaacccaa ggtcgcacag ttcagcggtg gggactagcg 7560 tcacgatgat gtactccgca tcgccaccca cttgcggcag gaagaacacc gaccgcgcgg 7620 cgggaacgac cagaacgtcg ccttcctgca tgttggtttt tagaaactta gtgttgttca 7680 cggagatgcc ggccatgccc tcgtttttga cacatattat ggtgacgtac gcggcgaccg 7740 tgggggccat gtggtggcgc atgtaccact cgtcgtgctt gagtttcaga ccgtgagatt 7800 cgccaacctc gaagtgcatg ttggcgtctc tgacgtagcg cgagaactcg ctgcgacaga 7860 ttcgcgcggg cgcccggtgg aacgtcgact cgaagagact gatggctgtc cattcgccca 7920 catgagtgac caccgaagaa gtgttttcga tccgagtctc gaacaccgag tccacgagca 7980 ccggacagtt ggttccgggc accgtcagca ccaagggccg cgcctccacg ggggcgacgg 8040 acgaagccac ggagtcggtg tccccgtacc cgtagtcgtc gtcggagtcg ccgcctccgt 8100 cggccccgtc gcgcggcctc cgcagcggca tgcagccggc ggtgggaacg cactggtttc 8160 ggccacggcc gaagcggcca aacagtctcg ccagggctga catccttgga cggccacacc 8220 aaaaccaaaa aaacatattt tatcagttat ttgtcgattt tcaccggctc accgagggca 8280 ggacctcctg gatcccggac acccccgcca ggcagcgggc cgcgcgctcg cgcacccaaa 8340 agcggtcgta gccgtgccgg agcacgaagg ccgccgtggc gtggcagtcc acgcgctcga 8400 tgaagccgtg gacggcgcgg cgcgcgtagc tcgccgcgaa ggcgcggacc accgccgagc 8460 agcgccccga gggcgagtcg tccgtctcca gcgccagcgg catgctcgcg atgcgcgaca 8520 tcaggttgga ggtctgcggg atgttgagct cgcgcgtggc ggtcatctgc gcctcgagcc 8580 cggccttgag cacctcgtcg cagcggcccc actccagcgc gcagaccacg cggatctcgt 8640 accccttgag ccgcagcgcg gtctcgatgt ccacggaggt gagcaccgcg ctgaagcgca 8700 ggcgctcttc gtccgcgggg tcgaagagca cggggatctt aacctccgcg ctgcgcgtga 8760 cctcgcagag cgcgatcgcg agcagcccgc gcgtgagctt gctcaccatg cgcggcttgc 8820 ccacggggta cagctggctc gcgacctcgc gcagcgggta cgccagtcgg aagcagcgcg 8880 cgtccgcggg caccgggctc gcgcccgtct cctcgaggaa gagcgcggcc tcaaccatgt 8940 tcagcgcgga gaagtgcacc gggcaggcgg cgcagccgcg cgcggcgttc gcgagcacca 9000 tctcgcgcag cccgcggaag gccgccatgt cgcaggaggg gaagatgcgc gcgagcgcgg 9060 cctggtgcgc gagcgccgcg tccgagagcg cctgcgcggc cgcggcggcg gcctcctcgg 9120 cggcggccgc gctctcgtcc gcggagacca cgtcttcggg cacgtccacg cagacgccgc 9180 cccagaactc gcagtactcg gagaagagcg tcgcgggcgc aaagcgcgcg aggtccacga 9240 aggcgacgcg gttgccgagc ctggagagca gcgtgttctc cgagatgcgc gtccagccct 9300 tgccggcgag ctccatgacc tgccgcgtgt cgaagaggga gctgtagaag ccgtacacgg 9360 tgatgttttc cttgcacgtc gtcagccaca tgaggaagtc gcgcaccacc agcttcgcgc 9420 agtctccgga gaacacgggg ccggcgttcg tcgcgatgga gttcaggcgc acggtgccgt 9480 cactgccgaa gcggtacacg aaccaggcgg ccacgctgtt gccagagggc gtgtgaacgt 9540 gtggctgcgc ccaggagtcg gcgctcgcgg cggtgcgcac gtcgtgcgag agcacctcgg 9600 tgtcggggcg cgagtaggtg ctggggtctt tgatccagat ggcgtagctg cccacgcagc 9660 acacgttcat gaggtcgagc agcgtctgcc ggcgcagcgg cgtgccgagc cggcgcacgg 9720 cgtcgtgcga gaccatgcgc aggtcgtaga ggcccacgtc cgagagccac tggttgagct 9780 cgtccatgga cagggcgtcg cgggggggcg ggctgtcttc gaaggcggcg cggagctcgg 9840 gctccgtctc cgcgcgctgc cgcaggatgt ccaggaaggg gctggaggag tcggggatgt 9900 agcagtcggg gtcgtgcctg gacactatag cgaaccgctg cgtcgcgggc ggcggggcta 9960 gcgcgtcggc gcgtgcgtcg atgaaggtgc acgatatacg cacggacttg agcgagggga 10020 ggacgactgc ggcggcgcgc gcgccctccg cgtcgaagat catcgtcttt ccgtccctcg 10080 cctttgcgag cgcgtattct ccaggcacga ggtccgtcgg cggcggctcg tcccaggcct 10140 gccggtcagg gacgccgccg cacacctttc cccagaaccc cagcatcctc caaaatacct 10200 ataaggacgg ccaatagcgg ggcttgcggg cgttcggacc ttccgcgctt taattttaat 10260 ttattggctt gcagaactcc gagcgccagt cccgctcgaa gaccgcggac aggtccttga 10320 cgatgtcgcc cttctcggcg ttcacgctca cgaaggcgtg gtagcggtag tgcgtgccgt 10380 cgaggttggc gaccgtgagg tgcgcgaagg tgtcgtccac gatgagcagc ttagtgttgt 10440 tcgcggcgtc gtcccggccg ggtaccacga acttgcgcac ggacatgtcc acgctgccga 10500 cgccaaagtc gtcgaggctg cgcgcggccg agaccgaaag cgggtccgcg ttcttccact 10560 cggtaatgat cacgcgcacg cgcacgccgc ggttgatggc cgcgcgcagc agcgcgtcaa 10620 tgatctgcgg ccagtactcc acggcgctgg cgtgcttgat caccggcacc atcgagagca 10680 gcgagaggtc gatgctgttc ttggcgttct cgatgcggtg cagcacgagg tcctcgtcga 10740 gcgtgcggta gaagcctagg aagcgctccg gcgagtccga gaagaatacg ccgcccccgg 10800 agtggtcgag gtggaagttc gtggccgtgg gcgtgacgat ggcgcagcag agccgcgtga 10860 acggcacctt cggctccacg atcatggagt agaaggtgtt gtagcggttc atgaggtccc 10920 aggccaggtg cttgttggtg gagtagagcc cgaggttctt gatggtggac acggacccgc 10980 ccgtgagcga ggcgcttccc acgtaccagt gcccggcgtc cgagagccag aagctgccga 11040 gaaggttgcc gacgccctcc ttggtggaca ccttgacctt gtagtagttg acgcccgcct 11100 cgcgcagctc gtccgcgtcc ttgtccttgc tctgcacgtc cacgagcagc gtgacgtcta 11160 cgccctcctt ggcgagcgtg cagagcttgt ccttgacgtc gacgccctcc ttggtggagc 11220 tcaggttgca gcagaagctg cagatgtaca agaacttctt cgcggactcg gcgatagcgg 11280 tgaagcagtc gagggtgctc atgttgccct gcgccaaaga cgccacctct gcgggcagcg 11340 tctccacgac gcggcagtcg gcgcccaggg ggatggagga gaacggccac atttatttat 11400 ctcacaaaaa taatagggct tcagggaaag tcttttagca ggcgggcgag ttcttcgagt 11460 tcgcttagga gttcttccat ttcttcggaa gtcagcaact ggagctcgga cttgatttga 11520 atatcttcga ggaaaccgtc tagcatgttc gccatgtctt ccggggagca ctgcgccaca 11580 tcttcgggga caggatcggg tgtgggcatt aggtctccgc ttacttgaac gtcgtccatc 11640 atcctgtcga tgaggtcttc gacttctaga cggggtccgt agatcagcat atttggtgat 11700 ggaggtagtt taaggtgcga gagttagtgt tatacgaccg ccaacgtgtg tttatcgcgc 11760 gtacattttc aataattaac aaactcccct tcctgcgcct gctcgagaag cagctcgtcc 11820 agctcctcct gtcggcgcgc ggccacgcgt ctttccgcga agagtaccat cagctccagc 11880 cccacgccgc acagacccag gacgccgaac accaccgccg ccgagatcga cagacccagc 11940 agcaccgaca tcctcacgcg ggcatccggc tatttaatcg ttctggaaac gtattaatat 12000 gggcgtcgtc atgtgcgggt gtctgtttgt gtgggcgggc tggatcgcgc gccgcgtgcg 12060 cggcctctgc gcggcgctgc gccagagggt gtcgcgcgac aagggctacg tggccgtcat 12120 ccagacctgc gacgacgact acttcacaga ggaggaggttc gacgacggca agcaggtggt 12180 cgcgctcctg cgcgacgtct cgcgcgtggt tgccgcgccc gcgggcgtga cggaataagt 12240 taggataagg agtcgagggg agaaaaacag cggtcacact ataaactcgc gcgaggccga 12300 tttgacgtg ctcatgtctg gaagctccgc tttctgcagc gcggagcggc acacgaagca 12360 cacttccgtg ttggtgggag ttatgcagtg gacgtggtag ccgtgcccgc acaccatgac 12420 ttggaacgga cacgcgccgg gacaggccgc gtttatgcat ccttccggcg agcgcttgtt 12480 gcagatgtag cacacgtctg agcacgccag cgtgcaggac acggccagct tccactgctt 12540 aaccttaacg ggcatggcta gttgaacacg accatgggcg agtcgcgagc ctcgagtcgg 12600 gggttcaggg caaaccgttt cacgccgtca acggttcttc tctttgcaat tttctctctg 12660 cacaggctcg tcagcgtcat ctcggccagg cgcgcgtcgt tgcctaggtg ccgcgcggcg 12720 tcctcgaccg tcacgcccgt cttgccggcc tcgtccatga gcacaatgca taccaggtgc 12780 gcgctagagc atatgacctc ctgctcgcgc ccgccggcag cggggatggt tagctccgcg 12840 cgcccgaagg ccgccagcgg cgccacgtcg taggcagtgt ctgctcgggc gagcgccgac 12900 tccacggcac cgcggagcga ctccggcggc gtcagcgcgg ccagcggcac cggcgtgggc 12960 acggtgtaca cgttcacggg catgagcacc atctccgggt cgtggtggcc gctctcttcg 13020 ccgtcgtgct ccatgggctg cggcggcggc agcagcggga gcagcagccg tccggacatg 13080 agccggcgca caaggtcgtt gagcgcggac gaggccatcg gcgggtacag ctccatggcc 13140 agcttcagcg ataggtgctt ctcgaggttg acgccggtgt agacgctctt cacgatgcgc 13200 gcgaaggcca cgcgcgcgaa ggccgccagc tcctcgcgcg gcaggcgctc gatgtaggag 13260 agcagcatgt cggtgtcgca cggcggcgcc gcgaccaccg cgccgtagag cgccttgccc 13320 gagagctttt ccagcgccct tgcgtgcagg ccgtgggtct tgagcacgtc cacgtagttc 13380 acgtacaggc agagcgcgcg atcgaggttg ctctccgcga cgtgcgtctc gatgcactcc 13440 acgatgagcg ggcccatgcg gtccttgatg aggtctatga gcccgccgta ggcgactcgc 13500 gcgctcatga ggcacgtgcg gcagtacgcc atcaggccct cgaggtccgc ggctatcacg 13560 tcctcgacca cgttcgccac gacgcgctgc cagagccgca ccttgctcac gttctggtgc 13620 cgcaccatgt ccacgagctc gtcgtacgag ccgccgggct cgtgcgcgcg atcgacgatg 13680 cacctcgcca tggtgcggct ctggcgcatg agctcgttcg tgaagcgcac gcacgcgtcc 13740 tcggagaaga gcgcgctcag gcaggagtag cagcggtccg cgacgaggtg cgggaagcgg 13800 cactccacga cgccgcggcc gatccgcagc acgcactcgc cgtacatctc gtccatggcc 13860 tcgcgcagac agtcgtccag cacgtccgcg ttgtgcgccc actggatcac gcagaggtag 13920 ggctcgatgt tctcgcgcgc gttttccacc tcctgcacca tgtactcgag cacggtcatg 13980 tcctcgtgga tgtcggtgcc cagcatgcgc ccgggcggca gccagctctt gcgcgcgatc 14040 gcctctcgca ggcacgccac cgccgtgaag gtgttgacgc ggagcttggt cagcagccgc 14100 cgcagtcggg agatgtgtgc cacggagagg tccatctcca tggcctgggc gatgaggcgc 14160 gtgagttcct cctccatggc ggcggctccg cgggcagata tacgcgaaca acggtaagcc 14220 gtgctatttc atttttggac aaaaagctag tcgtcgacgc gcatgttgtc gaggttccgg 14280 cacagcgaga gcacgtcgtc gcgcgcgcgc ctccggcgca gttgattgtt cgcgcgccgc 14340 gcgtccgcga gcgcctgtct gtacatcgcg gagtccgcgt acccgtgcag cggcgagcgc 14400 cgagcgccgg gcctcgggct cgcgcggcgc gggagcggcg ttggcgcgcg cctcgagcgc 14460 cgcgcgaagt gcgcctgcat ggccagcagg caaccgaacg gcaccatgta tcggtccatg 14520 aggcactggc tggccgcgga cggctcgcgc gggtgcatca cgccgccgcc cacgtcctcc 14580 atgacgtcgc gcagcacgca gcgcagcatg gtctccatgc cgtccacggg cttgaaccgc 14640 accggggagg cgtcgacgta gaagccgtcg gccacgaagt agagcgcgtc cagcccgccg 14700 agtttctcgc cgagaccgac gaagagctcg tccacgtgcc agtccaccac cgaggccttg 14760 aagagcacca cgtgccggat gtcgtgcgag cgcgcgagct cccaggtgtc ctcgccgatg 14820 ttgctggcgt cgatgcggcc tgtcatgcgc acgctcacgc acggcgtcat cccgttcttg 14880 tagcagaact ggcgcgcgag ctcctcctgg cgtacgatgt cgaccatgct ctccatgaag 14940 gaggtggaga gcagcatcgc gccgcgcgcg gcgcgggtcg cgttttcgtc cacctccact 15000 tccatcccgc cgccgatcct aatcatctat cgtatttaaa ttttcggcgg agcagacacg 15060 cggctgctcg ctgcgcgatc gcttcagccg cggcggcgtc acgcacgcgt tgcggcggcc 15120 ggcacgcacg gacgaccgcc ggggctcttc gctgagcgag cgccgcggcc gcgtgacgcg 15180 acagtcgcag gtgggttgcc gggagtcgct cgcgcgcctt cttcgcattt cgccggaacg 15240 ccgcgtttat gtaggggatt atattttcaa cgtaactaaa tggacggggg cgtgcacaaa 15300 cggcctttca tcgtgaacgt ggatggcatg ggcaaggtgc tcgtgctccg gtacttgcgg 15360 atgtgcgagg tgcccgaggc caagtgcgag ggctcgcgcg cgtcctgcgt gctcaagatg 15420 gaccctcccc gctcacccag ctgcgagcgc aggccgtctc tcccgccgtc ccccccatgc 15480 cccatgcgca cgcctcccgg gtcgccgctc caggctccct tgatgcgcac gcagatgctc 15540 caggggctgt tcgacgctgc caaaaacaac ggcgagcaga tgtgccgccg ccagtaacct 15600 aggctgcgca gtacgaaagt tagtgcgtga tcacgttttt tgcaatgtcg atcacgccgt 15660 gcgtgcccgt cttgcgctcg cgctccacca cgctagtcac gggccgcgcg tccgagacta 15720 gcgaccccag catcgagcgc acggcgccct ccgcggcggg gtggcgcgtc agcagcagga 15780 acatcacgat gtgcgcggag acgccgcgcc ggctcagatc gtgcacggcg tcgccgtcca 15840 tgagcacggt gttcgagaag tacgtgaaca gagtgttgtc tcgcaccagg aaggccgagt 15900 tcgagacgct ctcgaagtcc acgatctcgt cgtcctgcac gcccatgtcc aacagcgtct 15960 gcacgagcgc gggctcgtcc aggaacacca ctgcgcgcgc gaacccgcag tccagcgcgc 16020 gcgcgtccgc ctccaacacg cgcgaggcgc cgccctccgg cggcaggaag gcgcagggca 16080 gcggcgtgcg tccgtccgcc ggcgcctccc cgagctcctc gagcgcgaag gccagcagcg 16140 tctccatgcg cgcgcgcgcc ttgtcgaagt tgtccgcgag gtcgcggatg cggtctgtct 16200 gcgagaacat cttcagcatc gccatgagct gcacgaaggg gtgcagcacg tatatgttgt 16260 ccacgagcag cgtgggcagc gcgcgcagcg tggcctgccg cacgttgaag ctgtccagga 16320 tgtgcccgcc ctcctcgtcc tgcagcacca cgtagttctt caggtagggc acgcgcagca 16380 gcacggtctg ccgccccgtg acgaagtata tcaggaaggc gaggttgatc aggaacgggc 16440 gcgcgttcgt ctgcaccatg tcgatgtcgc cgtactctat ctcggggttc agcaggtgca 16500 gggcgtacga gccgtagcac acgcaccgct tgttgtgtcg gcgcaggtgc tccttcacga 16560 gccgcttgac cacctccacc aggtccgagt gcttgtgccg cgccatcggc gcggcctcct 16620 cgggcggcgg cagcactgcg tacgagttga gcgcgcggct ggcgagcgcg cgcgcgcggg 16680 gcgcgtccac gcgccgcacc gccgcgttga ttgcaggcgt cggcgtcgtg agagagccca 16740 gcgtgcgcgt gaactcgctc acgatcacgc tctgcagctc cagcaccgtc aggatctggc 16800 ccagcttctc caggcgccgc tgcctcgaga agtactcctc gatgcgcgcg gcgatctcct 16860 tctcggagcc gcctagcttc ttgaagaagc gacgacgact ctttacaaca agagagagaa 16920 aaagcttcct atcgaagttg aggacgcggg tcatgttgcg gcgctgcgcg cgcaggagca 16980 cgcagcgctc catggagggg cgcgagccga ggtactcttc gatcacgggt ggagccatga 17040 cagctatttt ctgaacccgc gattattgta cagcgcaagc cgcgcgcaga cctgctggca 17100 cagcagcgtc gtgtttcgca tgcacacgcg cgaggactcg atcgtgcgcg cgtccggtgc 17160 ccaggcgcgc agctccatca gttcctgctc gacgaagtcc acgggctcca cgaagcgctc 17220 tgcgcagagt ccgtccgtga acgcgttgac gatctgccgc acgagcacta ccacgtccac 17280 ctgctccacg aggcgcacgc ccatggcgac gtgcacgaag aggcagcgga agagcgcgtc 17340 catggccatc tggtggtccg agcagggccc gaccgcggtc ttgcagccca gcgcgaagcg 17400 cccgatgccg cggtactgca ccatctccga gggcgagaag gagagccgct ccatcttgag 17460 cacgggcggc gggcccgccg gcagtccgcg cgcgaggtcc agcaccggcg tccacccggg 17520 cgtgaacatg tccgggatca ggaagagccc gtagctggcc atgcgcgcga tgtcgaaggc 17580 gtggtccacg accttgttca cggcgctgtc cgcgcggttt acgcgcagcg cctgcaggat 17640 cacgtttccg gaagcgtgcc gcgtgatcgc gaggtccgcg gtcgcgtacc cgcgcaggcc 17700 cggcaccgcg tacgcggtca gacacacggc caggcgcgcg ctgtgctccg aggagaagat 17760 ctcctgctcg tagccctcct cgggctcctc gcactcgcga gggcgccgca cgtcctcgac 17820 cgagcgcagc cgcatctctc cctccgacac cagacagcca agcgactccc tcaccgccgg 17880 cgcgagcacc tccgtggcgc agagcgcgtc gtgcacgcgc ttgagtgtgt tcggcttcag 17940 cgcgtagccg aagagcagcc gcgtcatccg cgagcccgag aacgcgaagc ggcgcacgta 18000 ctcctccgcg agctcggggc ggtcgttgat ccacgaggta gagaagacgt ggtcggaggc 18060 gaaggggtct gcaccaaccg cgagcagtgt ggacagaggt acggtgtcga ggaagtccac 18120 gacgtcgggg aagttctggc gcacgcaggc ctcggcgacg cgtctggtgt gcacgcacat 18180 gtcggtgacg ggcacccggt ggccggactc cacgacggac acgcagacgt cctcggtgac 18240 ggcgtccacg ggcatggtcc gcagcagctt gccgagcacg tcgccgaacc cgccctcgag 18300 cgccttgcgc cacacgaacc ccgcgtcgaa cttcccgggg aagtccgcga tcaccgaaag 18360 ctccgcgtgc gagaggttgt ccacgttgag gtaggtggcg gcgtccacga agatgggccc 18420 gaaggcgccg gtgtcggaga cgcggtctct gaggtagtcc ctggcgtagt ggaggtactc 18480 ccgcacctgg ccggcgcgga tgcgctcgag cgcgaaggcc ttcatggtct cggagcagag 18540 cacggagtgc cgcagcccgt ccagtgtgcg ccgcacgtcg tagacgccgc gcatctgcgc 18600 gagcatctcg acggcgtccg ccggcgtcgc cgccgcgagc cccgggttca ctggaggtat 18660 cctgtgttct gcgagcatgc gcttgaggaa acagaggtcc agcggccgcg tggtgtacag 18720 cgcggaggcc atctcggggc gcgtctcgac gatgtcctcg atcatctcgt ccgtgaatgc 18780 cgcgttgatg ttgtgcacgc tgcgcgcgtt cacgtgcagg aggatgtcgc ccacgttgtc 18840 ggggaatcgc tcctcgatga gccggacgtc gtcctccgtg atgttcatgt agggaataca 18900 gcggcagagc agcgcgtagt ccgcgaactg cgcgatgtag ggcgtgtgga actcgatgtg 18960 tctggcgaag agcgcgccgc agcgccgccg cgagagctct tcgagcaggt cctcgggcgt 19020 gacgtgctgc gggcggaaga ggtgcaggtg cgtggggtgc tcggcggcca cgcgcgcgta 19080 cagccgccgc gggaggtgtc tggggtgcac gccggcgagc acgagatcca tggcctctga 19140 ggtagacagt gcggcgaacg cgcgctcggt gccgcccgcg gcgacagcgg cgccgacaaa 19200 tctcttgagc agctgcagca tcgcgtgttt gggctttcgc ggaaggcgct tattttaatg 19260 ttattggcgg tggccggtgc gagataaaaa ttagaactga tgccgcagtt gttgatgata 19320 tgatgattgc gctggccggc gcgagataaa aattagaagc tgatgccgca gttgttgatg 19380 aggatggtga gtgcgctgga gcaagcggtg tggcgcgcta gcttcttgct ggccccgtcg 19440 gccacggcaa cgacctttcc ggatatcgtg atggtgcagg tgaagcgcgg acagtgatcc 19500 tctccgccag cacgcgtctc gcagaactcc agaggtctgt gtgtcatcat gcagaactcg 19560 ttgaccgcgc tgaccgggtt aagacttttg aggcgtatca cggcagactg agtcatgatg 19620 tcgatgtcgc cgccgaaaag cgtatcgcac ccagcctcgg tctccatggg ctcggtgtcg 19680 gagttttcgt cctcctcggt gggcgcggag ggcgcgcact ctacgaacca gcggggcggg 19740 tttccgtcct cacagcaaac ctcgtccgag tccagcaggc ggtacagctg gcggtttgcc 19800 tcgtgtttgg atatgccgag ctccttcgcg atttgcttgg ccggcagctt gtcgtcggat 19860 tttctgagaa gctcgaggat cagagacgcg cactcgcagg ccattgtggc gatttacggg 19920 gcgtgcgttt ttttaggatt ttggcttgcc tttcttttcg cagaacttgg gaggattgaa 19980 actcttttgg caatttttgc aggcgtactt gatcaagggc ggctcgtccg ccgagcgcgt 20040 ctggatcatc atcggcatgg tgttcttgct ctggcacgag gggcagggca ggttgaactt 20100 ctcgtcgagc acgttgaagt acccgctgta gtcgtggtcc ggcacctcct cgatgtcgta 20160 gggcacgcgc gcggccacgc acttgaccgc gaagagcagg taccgcagcg cgtcgtgctc 20220 cgcgccgctg gtcgcgcgga tctgcgcgca caggtccgcg tagtcctcgt tcgcgtccac 20280 ctccaggctg cgcttgttct tgtacgagag ccggttcttg gcgtccttcg agtactcgat 20340 gccgatgttg tgcgcggggt caaagttggt ctcgtcggtg ttcgaggtct tggtgttcac 20400 gatgttcttc agcgcgaagc gctgcgcgca gtccagcgcc catcgcgcga tgcgcgcggc 20460 ctccgccgcg tcggtgtgct tcgccgcgag gtcgcgcagc cggtcttcgt ccatcgcccg 20520 attttaggtt gggtatatta tctcaattcc gctcttccgc gggccgcggg cgcgcgcccg 20580 cggcaaatta ggcgttacaa atggacttcg tgcggcggaa gtacatgata cacgccatcg 20640 accgcaacct cgacttcatg aaggccgagg tccagcagaa ggtctccatc ttctccctcg 20700 ggcacgtgct cgcgctccac tacctggtca ccgcctttcc gcaggcggtc atcaccaagg 20760 acgtgctcgc gagcacaaac ttcttcgtgt tcgtgcacat gtcgcagcgg cacgaggtct 20820 tcgacgccgt gctcaaggcg gccttcgacg cgcctcagct ctttgtgcgg gcgctctcgc 20880 ggcacttcga ggccttcgtt gccgccatcc gggcctaccg cgcgacctgc gcggagctgc 20940 tggccgacgc gcgcttcatg gaggtggctg cgcgcgcggc cgagctcgcg gaggtcattg 21000 gcgtgaacca cgacatcgcc gcgaacccgc tcttcgcgga cggcgagccc gtgcgcgacg 21060 cggagctcat tttcgcaaag accttccgca agaccgagtt ccgcgccgtc aagcgcctcg 21120 ccgtgctgcg gctgctggtc tgggccttcc tcgtgaagaa ggaccttggc ggcgagtacg 21180 cggacaacga ccgccaggac ctgtttacgc tgctgcagaa ggccgcgggg cccgtgcgcc 21240 acagcgcgct cacagagagc atccgcgagt acctcttccc cggagacagg cccagccact 21300 gggtctggct gaacgcgcgc gtggccgacg acgcagaggt gtaccgcgac cggcccgcgc 21360 gcacgctcta cgagcgcgtg ctcagctacg cgtactcaga ggtcaagcag gggcgcgtga 21420 acgccaacac gctcaagctc gtgtaccggc tcgaggacga ccccgacatc aagggtctgc 21480 tgctgcagct catctacgac gtgcccgcgg acatcgtcgg cgtcgtggac tccgcgaacg 21540 aggagtggcg gagctacttc gtgagtctgt accgcgagaa cttcgtcgac ggacgcacct 21600 tcacctcgga cgcgcgcttc cgcgacgacc tcttccgcgt ggtcgccgcc gtcgatcccg 21660 acttcttcga gcccgagcgc atccgcgagg ccttcagcgc agacgcgcgg ctgcgagagc 21720 gcttcacgga catggacctc aacaacgcct tcatgtcgca cctcatctac gactccgtgg 21780 accccgacgt cgccgccgcc gagcgcgggc tcgcactgcg cgtgcacaac gaggactccg 21840 actacttcat ccgggagtac aacacctacc tcttcctcag cgagaaggac ccgctggtgc 21900 tggaccgcgg ggcgctcacg cggctctcgg acgtccccgc cgagcgcttc cgcgacctct 21960 tcagcgacag tgtgctgcgg tacttcctgg acgcgaagct gggcacgctc gggctggtgc 22020 tcgaggacta ccgcgaggac gtggtcgccg ccatgcttcg gcacctgcgc cgcgtcgagg 22080 acgtgtcttc cttcgtgacg tacgccgcgc gcaagaaccc cgcctgcgtt cccggcgtcg 22140 tgcgcgcggt cgtgagcaac ttcaaccccg cggtggtcgc ggccatgcgc cccttcctgc 22200 gcgagcacat gacgcgcgtg gacgcgctgc tggacggaat gccgcacctc tcggaggccg 22260 accgtcggta catccgccgc gtggtgctgc agggccgcgc ctgattcgcc gtcaataaat 22320 cgcgatggtg gacagcggca cgcacgacgt ggactccgcc gcgcaggagc gcacgcccaa 22380 ccagcagacc ttcttcacca aggggctcag tccgctgatg cgccacacct acatctacaa 22440 caactacgcc tacggctgga ttcccgagac cgcgctctgg agcagccgtc tgggcgacta 22500 ccgcgtcacg gacttctacc cgatctcgct gggcatgctc aagaagttcg agttcatgtt 22560 ctcgctgctg gcggaccccg gcggcgcctg ccccgcgtac gagcccaagc tcaacaccga 22620 gttcctgaac cgcggctcct tctcgggacg gtacgtgaac cccttccacc gcttcgcggc 22680 gctgcccgag cgcgagtaca tatccttcct gctgctgagc tcggtgccca tcttcaacat 22740 cctcttctgg tttaagggcg agaccttcga cactgccaag cacagcctgc tcggcgccgt 22800 gtacaccacg cccgagcggc acatcgagct cgcgcggtac ctgcggcgca cgggcgacta 22860 caagccgctg ttcagccgcc tgggcaacga cgacacctac tcgaagccct tctctgggtt 22920 cacgcgcatc agcaacccca cgcccatcgg gcggctgccg ccctcggact tcgagacgct 22980 ggccaacctg agcaccattc tctactacac gcgctacgac ccggtgctct gtttcctggt 23040 cttctacgtg ccggggctct ccgcgaccac gaagatcacg cccggcgtgg agttcctcat 23100 ggagaagctc tcgctcgcgc ccgagaacgt ggtgctgctg tagcctcaaa cataaaatat 23160 aggcgccttt gatcgcactg cttcagttca gacagagcta agatggcttc ctacatcagc 23220 ggcgctagcg ccagcgcgaa caccgcccag ggcggcgatt ctcagtaccc acagtactat 23280 tatcacacac gcacctccca aggcgacatc cgcgacgaaa gcgaaggttg cttccacacc 23340 acggacgacg agcacttgga tctgtccgac gactacctcg gcgatggcgc accacactgc 23400 ggacacagcc acaaccacag tcgcagagat ggagatcggc accgccagcg cgcaccgcgg 23460 ctctatgagg acccggtgcc cgcgaacatc atggtgccca cgctcagtct agagcagctg 23520 ctggaggaaa cctcggtcgc ggggggcctt ctcggcggca ggacagagag ggacgtgggaa 23580 cagctcctgg aggagttctc cgcactctgt cccggggacc agatcaccgc gctgcgctgc 23640 atggcggcct ccttttaccg cgacgcgctg ttcgcgccgt acgcctgcat gcacctcatc 23700 gccagtcgga tgcgcgtgca ctacgcgcgc gaggtcgtgc acgtggccga ggacctcgcg 23760 gacgcgatgt ctgcgaacag cggcgtctgc ttccggcggt accgaaagcg cgtgctagag 23820 gacatgctcg cggaggagat gggcgtgtac aattacctcg cgcgcgccaa cgcggacatc 23880 tgcgaggaca acctgctatc ggccgtggag acgctgctgc ggcgcttccg tcggatgggc 23940 tgctaccgct ctctgtgcat gctcaagatc ctcgcgctgc agcacgagga cctggccggc 24000 ttcatccgcc gcagcataag aaaaacctgc aacttggcac acgcgcgcac gcacacggtt 24060 tacgtgtagt taccctgtaa agacgggctt gctcccgaac aagcgctcga agaagagcgt 24120 gcacatagcc ttattgtcca gcaagttgac tatctctgta cacagcctct tgaagtacac 24180 ctcgtacatg atccgctcgt ttttatccag tctgaaggtc ttgtcgacca cgcgctcgta 24240 ggacttcacg ttcgcgatcc ggcgccgcca ggggccctcc tcgcacacgt acgcgaagaa 24300 gtagcgctcg ccgatctcga tggcctccgc gttcgccgcg ttgtaccgcg tcactagcgc 24360 cacgttgggg ttgtcggggg acttgaagtt cttgtggtgc gttcggctca gcaggaacca 24420 gtccagcggc atgctgcgcg cctcgaactc gaaggtgagc tcgtcctcca gcgagcgcag 24480 gatctccacg cccacgttcc cggagccctc ctccgccagc gcgcggcaga gcatgtcctt 24540 gtacttgcgg atcatgagct tgtggaaggg cgccacgtcg cggcgcgtct cgctggtgcc 24600 cttgctcacg cgctcgctgc cgccgccgtc gctcaccgca aacttgatcg tggtgtactt 24660 cttcttggac tgcatgatca ggttgcagta caccgcttcg aactccacct tgaagttcgc 24720 gaagagcacg tgctcgttga tcacgcgctc cagacagcgc cccacgcgcc gcgagaacgc 24780 gatgtcggag gcgcccacct ccaggaacac ggagtcggtg tcgccgtaca cgctgcggaa 24840 gcccacgcgc tccgtgcgct cgccggccac cgccgcgtcg atctctagct ccgcggcgcg 24900 gcccgcgaag gcctcgtcgc gcagcagcgg gttgtccggc gccgccgcca gcgacagccg 24960 cgtgccgcac accgacgcgc cgtctagcgt gcgctccagg tacgcgatca tggtgcgccc 25020 gatggccgtg cagctcttgg ccgaggcgta cgagaagagc gcgctgttgc ggaagcccat 25080 gaccccgtac acggagttgg ccgtgatctt gtacgtgtac tgcatcgagt tgtagatctc 25140 gcggtccacc gcggtctccg cggccttcat cagcttcttg tacttggcgc gcgcgtccag 25200 gaaggagcgc agcagcatcg ggatgatgcc cttggcctcg cggtcgaaga tggccacctc 25260 ggcgacgagc tccggcgagc gcggctcgca gggcaccgcg atgtaccgcg gcgccgggaa 25320 catccgccgg acgtccacgg ccgcgacctc cgcgtcgagc cggttgtccg agacgaccac 25380 gccgacaagc gtctccggcg acaggttcgc gtagatgcac acgttcgggt acaggctgtt 25440 gtagtcgaag atgagcacgt gcttgttgtg catcttctgc ttgggcgcca tcacgcggcc 25500 gccctcgtag aagaacttgg acttcgtgtc cgcgcgcacc atcaccgtgc ggttctccag 25560 cagcagcttc atcagcgggc ccttgatgca ggtgctcgcg cggtactcga agaccacgct 25620 ctgcggcagc aggtacgtgg acgcggcggc cgcgatcttg gtctccacgc cgtagtgcga 25680 ccagaggtag aggcagaggc aggcgtcgtg caggcagtac cgcgccatgt ccagacacac 25740 gtccagcgag tagttcgcgt acatgtccgc gaggctgacg tcgtccttgc cgaaggccag 25800 cgtgacgcgg tcgccgggcg cgcgcgccgc ggggtccgcg aggtccacgg tgaagccgtc 25860 ctcgtcgacg cgtttgtgca gcacgcggca cacgcgctcg tccacggtca cgtagttgcc 25920 ggtgctgagc acgcgagcga acacggccgc gttcccgtcg gcgtcggtgc tgcggtcgcc 25980 gcgaaagcgg accgcgtccg gccgcgcgtc ctccacgacc gcggtgcagt ggaaggcgtt 26040 cttggatatg gcgtccagct tgtaggagtc cagcttctcg gtgcgctgga tgaaggcgta 26100 caggtcgaag tagatggtcc cgttgttgtt gttgatgtgg aaggtggtgc tcgagacgcc 26160 gccgacgccc ttgtggctgg acttcgtgcg ctcgtacacg cagaagttga ctgtctcggt 26220 cccgtccggc agccggaagc ggatgtgctc gcccgtgagc agcgacagcc gcgagtccag 26280 gtaccgcagg tcgaagttgt ggccgttgaa ggtgaccacg aagtccagcg gcatctcgag 26340 caggcgcttg gccacgcgca gcagcgtcac ctcgggacac agcgtgacct ccgcgtcgaa 26400 cttcacgtcc gccgggtcca ggcagaccgg gatctcgcgc cgtgccgcct cctcgaggtc 26460 cgcgtcggag agcatatcgg agttcgtaag cgtgaatcgc cgctccgcgc cgtccttgtc 26520 caccacgcag aagctgatgt gcgagacggc gttcttgaag acggaaggaa actttttctc 26580 gaagtggcac tctatgtcga ggaagagccc cgagcgcgtc acgttgaagc gcgggatctt 26640 ctccgcgaag cacgcgccgg ggtcgtcgca gtggaagcag ttgctcccca ggtcgcgcag 26700 cagcgcgggg tccacgcggt agcacccgtc agggtcgatg tcgtgcgcca cgaagaacca 26760 ggacacgttc agaaagtcgg acatgaagac ctctggcggc gcgagcttgc gctcgctggc 26820 caccagacac agctctatct ccgagcgctg gcgctccgga atcttcgccg agcgcgctac 26880 gatctcgtcg atgctgacca cggacatggg cccgagcgcg cgcgtccacg ccagcggctg 26940 ggcgatgtcg gccaccgcgt ccgcgcgcac cacgtagtaa aagtgctgca cgaagcgcag 27000 gtacacgacg gcgttgtcgg cgcggcgcgc cttgaggaag aggaaccggc tgtcattgcc 27060 gcggttctcg aaccagttca aacatttcag ctccatttca aagagcataa taacatttca 27120 tttaaatgga gcctcgcttc tggggccgcg ccatgtgggc ggtgatcttc atcgtgctgc 27180 ggcgcttcga ggagcaccgc gacctcgagc gctgcaagcg gcagctgtac gtgatctgct 27240 ccacgctgcc ctgcatcgcg tgccgacgac acgccaccgc cgccatcgag aaaaacaacg 27300 tcctctccag cgaggacccc aactacgtgc tcttcttctt catcaagctc ttcaacaacc 27360 tcgccttcga cgacagatac aagatcgacc ccgcgaaggt gcgcccgctc gtctagagca 27420 tgccctcgta cgcgcgcgag ttgtccgagt acacggtcac cgcgatgccc tcgcgcggcg 27480 tcacgtgcac gtgcatggag tccgtgatca cgaagcccac gcccgtgacc ggctcctcgc 27540 ccgcgtcgtc cgtgaagagc agcccgtggt tgaagaggta gaactcgttc tctgcgagcg 27600 aaagccgccc gcggtcgcag aggtagtaga agatgtcgta gtcgcgcacg gccagcgtga 27660 acgtggactc gctcaccacg atgtacttgt ccagctcctc cagcacggac gcggccgcgc 27720 ggcgcgcggt ggcgcggcac tgcgtcgggc actcgcacgt gtctgcagag tacaggatgc 27780 gcgttcgccc cgaggcggtc tcgagaaaaa cgttaatcgc ctccatcgcc cagaagcgac 27840 tcgaggatcg cgagcaccgt gcgcagcacg agcccgatgg tgcagaaggg aacctctccc 27900 gactccgagc actcgcggat ctccgtctcc acgcggtcgt gcacttttat ggagggagcc 27960 gtcgttccag tggcctccat cgcgacggac accaccttgg ccacgaactc gcggatcttg 28020 ctcatgcgcc ggagcacggt cacgcggaag aagacggccg cgagcaggta ctcggccacg 28080 cagctcacgg cgatgagcgc ctgcgcgtgc ctggtgttga gcacgtgcgc gtcgggcacg 28140 aagtccgaga tcttcaggtg cgagagccgc acgagcgcgt tggtgtcctt gacgccgtcg 28200 caggaaatgt tcgcgaagat gagcttctcg tagtcgagcg cctcgaccac gcgctgcgcg 28260 tccatgtgcc gctcgcccga gagcgcgcgg ctcaaagggc cccagcacac cgagcccgcg 28320 aagcaggggt ccaccacgcc gtgcatcgcc agcagcgtca cgtcggccac cgccgcgagg 28380 atggccgcgt cgtcgagctc gttcgcgggc gtcgcgcccg tcagggacgc gctgcgcagc 28440 gcggacccgc ccggcgccgc gtgccgcgcg cagaactcgc acccgcagcc cggcggcagc 28500 ggcggcttcg agagcagact tatgagcccg cccacgtgcc cgtgctcggt gatcagaagc 28560 gccaggatgc tgtcggtgct gccctctatg gcggctgtgg ccgcgctaga aggctctccc 28620 gtgacctgcc atccgcagac aaccttgagc atcttgcgct tgagctcgtt gggcgcctcc 28680 gaggccagca tcgtgcgcgg gaacgtcgcg ttgaggcgga agtcctgcag cagcttttcg 28740 agcgtcgcgg tcttggcgtg ccgccctttg cgccactcct cccccaggtg ccacatgagc 28800 28860 atcagcggct ccgaggcgcg gaagctgccg cgcgcgtgca ggcgcatgga cgcagacgag 28920 gaccgcatcg agggtctctg gtggaagctc gtcatcgtga agcgccgcgt gagcggacct 28980 acctcgtcgc gcgactcgtc gaagtccggg tcagggtccg tcgtgtcggt ctcggcgctg 29040 29100 gtgctgaagc tgcgcgagca ggagtccgcc gtgtccgctt cctcgtagtg gaagtccacg 29160 tgctcctccg gcagccggcg cgagcgcgac ttggagatgc cgaccatctt gtccgcgccg 29220 accgggcgca cgcagagcgc catcgcgccc tcgcgcaccg cctgcgcgaa ctcgcggctg 29280 gcaaccatgc tggggttgag gaacttgatg atgttgaagt atggccactc gcagacgagc 29340 cgcgcgcagg tcgcgacgtc gtcgacgctt ctgagggccc tgttcagcgg ggggatgttg 29400 ctgccgtcgg ccagtgcgac gaggtcctcg ggggagatct cgagcttggg aatcatctcg 29460 ttcacgagcg cggggtcgat ggcgtggcag acggtctcta cctcggtgcg cgagagcttg 29520 agctgcgcgc aggccgccca cggcgcgcac gtgagcgcga acaccgcgga gactcggccc 29580 ttgccgacca tcgccacaac ctcgggctcg tagaccaggc cggccttgag cagagcctcg 29640 agcacctcta tgtcgtcggc ggcgagcagc gcgcgcctgt ggaagcacac cgcgggcatc 29700 atcttcttgc agatgccgcg ggtgctcttg agggccgtga taaggtcggg gagcctgacg 29760 tgctgcggct ggaagaacat gacgttggcg gggctcgcgg ccaccgcctc gtcgtacacc 29820 gacatcggca ggtcgccgtg gagcccgcac ggcagcaggc tcagcagctg cgcgcgcgag 29880 agcttctcgg cgcagaagtt cttcttggcc agggcggccg ccgcgtcgcg ggccttcttg 29940 gggtataaca acatggcggg ctttaaacac gaaacaaaaa tccgggttgt aacatttcaa 30000 ttttgcatgt tctgggcctc ctcgcagagt ttctccaggc cgccggccac gatggcgtcg 30060 acgaagaggt cggcctcggt gaagcggtgg ttgccgcgca ccgccaccag cgcgttctcg 30120 gtgaccacca ccgacagctg ctgcgcagcc gtgcgcaggt cgaagtgtcg gcacgcgagc 30180 ccgtggccca gagtctggtc cagcgccgcg agcacctcct ccaggctctc ctcgcggtgg 30240 ttgtagaacc acatcagcac gaagtaggcc acgtaggtgt agaggtagtg cgcgaccgcg 30300 cgggcgcgca ccagcggctg gttgcagcgc gcgaaggcca ttccgctggc gatgaggtcg 30360 tcgtccagcg tggcgtagtc gccccagttg agcgcgctga actgcacgct gtagaccgcg 30420 cgcacgaacc cggactcgag gatgtcgatc tgcgacggcg cgccccaggt caccagccgg 30480 tacacgatgc cgcgctgcat cagccgcatg aggtcgccgc cgacctcgcg caggcggtgc 30540 gtcagcgagg cgaaggccag cttccgctgc gtgtactgca ggcccacggc cacgcacccg 30600 tccgactcca ccagcacgag cttgtggtcc gtgcagccgt cgctgcgcag gccgccctcg 30660 cgcgccatca tgtcggtgac gaacatgtac ttgcgcgcgc gcggcccgac caggatgcgc 30720 ttcttgcctt ccatgcgcag caccacgtcc tctagcagcc gcgtgctgtc cacgcgctcc 30780 acctgcgggt ggatggtggg ctggtagttg tacagcagcc gcggggacca gttgtaggcg 30840 aacgcgaaga ggtgcgtgtc caggagagag atggggaaga cgccgccttc ggtggcgcgc 30900 cggaggatgg cgagcttggt ctccgcgggc agcaggctcc cggtcaccgc gccgaagaac 30960 atggggtggt tgcggaactt gagcgcgtac gcgctcagca cctcctctcg cgagaatatc 31020 gagtccgcgg ggttggagct cgcgggcagg agcacgtcct ccacgctcag cacctcgtcg 31080 atgaagggca gcaccatgtc cacgttggag gcggtgaacc actccatgtc cacggcgttg 31140 cgctccacga tcacccggat cgtctcctcg gatatgttct cggcgaaggc gctctgcagc 31200 tcgatcaggt tctcggtggc gtcgatgctg agcccgaggc gcatgccctg ttgcagcacg 31260 tcgttgatgg ggttcacgta catggccacc gccatgcacc cggccggctg cacgcgccag 31320 aggttggagt acgcggacac gtccgtgatg cgcagcgtct ccagcacgtt gtacatcgcc 31380 gcgcgcattt ccagcgtgtc cacgtacacc tccgcgtgct cgaagatgat gtcgagctcg 31440 aacgcggaca gcggcagact cacgtagatc tggcaggcgt caaagagttc ctgcgcgtac 31500 tcagagaagc acgcgtacgc gatcacgccc gcgcggttga cgatgtagtc cgccttgaac 31560 atcttcgtga ggtaggcgta cagcgaccgg caggccacgt gcggccttag ctcgtcgagc 31620 acggcgtcca gcacctcgcg gtgctgcagc acggaggggt gcaggaactg cgtgaagtcc 31680 accgcggtct catccatgaa gtcggggatg gtctcgacca ccaagcggtg gttccgcacc 31740 gcgcggaagc cggtgttcat cggcgcgatg ctgtgctggt cgtggacctc cagcaggatc 31800 tcgtagccga tctctcggca gctcagcgcc gcgcgcgcct ccgtcacgct cgcgttccgg 31860 aagaactgcc gcaggtgctc gtccgtgcgg cagagcgtga cggattgggg gatgcgggaa 31920 aggtcgcaaa gagggctgtg gacggagatg cgccgcagcg cgtggtctac gaactcaaaa 31980 ccgcgcctcg acatcgtgaa gtcgcggagg gcgtacatgt tgtaggaaca gaggcggaag 32040 aggcagtcta tgtctagcat gttggaaacg cagtacgcgt gtctgtggag gtgcgggagc 32100 atggcgggca cgacctcggt cgtgttctgg agcatggtgc atacgaggtc gggcgctgtg 32160 aggtcggggg tgacgatgag gatgcaggag ctggagaact tgctgagctc ggaggccagc 32220 cggtgaaggt tgtagtcgtg gcgctggctg aagttgctgt ttatcgtgcc cgtgaagccc 32280 atgagcgccg ccagcgtcag gtcctcgcgc tcgatggccc agatgtctag gccggaggct 32340 atcatgcagc gcaccagcgc ggcggcgcgg tcgctcgtgg ggtagctcat ggtgctgtcg 32400 gtcgtgcgaa tcagcatggg ataatgcttc atttttacgg tcgggggttg cggactgtgg 32460 ggcgcacagg gcctgcgggc ggctcgtgcc ggtccgcggc gttcgccgaa cgcaggaacg 32520 ggcccatgcg cgcccaggcc atccacagcc ccgccgtcag cgccagcagc cagacgaata 32580 ccacgatcat cttttatgta gctggaactc gcgctcactc cccgccgcac ggcgacgggg 32640 agagcccaga gccgagctcc atgcgcgtgc tctgcacggt gagcgactcc acgagcttgg 32700 acacgttcat gcgcgtgttg tcgggcacca ggtgcgcgag gcgcgcgtac acgtcatcgt 32760 gcatgcgctt gctgcagcgg tccaggctcg cggagagcgc ggagactagc gcggtgtgct 32820 tcgcgtacac gaagtcgccg agacacacgg tctcgagccc gagcacgtcg gcgctctccg 32880 cgtccttgag cgccacgaat atcttctgct cctcgcgcgt catcgagcgc atgaggtagt 32940 cgtgcagccg cgagcgcgag atgagcccct gagagatctg cgggctgcgc atgaagcgcc 33000 ggcgcatcgc gcacagcagc tcctcgtcga cgacgtacat gctgtccttg atggagctct 33060 tctcgtcgat cacgagcaga ccgtcgttgg cgaccacgtt gatgaaatcg tccacgtgcc 33120 gcgcgtctat gtcgtagcgc gtgccgccgc actcgatgtg cgagggcggc gacttgagcc 33180 ggttcgcgag cgccttcacg tcggagacgt cgatgtacag cgaggactcg cgcgggacgc 33240 agccgaggat gcgcgtctcg agcggcgtga ggatgagcac gcgctcggcg ccgtcgacga 33300 gcttgccgtc gtcgggggaa aagaagttgt tctccacgat gctcgagacg aggctggcga 33360 gcacgccgtc gcggtaggcg ccgagcgcaa actcctgcac aaagggcgcg tgcagcaagt 33420 ccacgggaat gcgcatctcc acgcggcgcg cgaccgactt cttcttctgc aggtgccgcc 33480 ggtccaccat ctcgtccacg atgtccgata tgcgggagca gaggtacgcc ttgaggacgt 33540 tggcgtttac cttgttgaag atgagccgtt cgtcctccat ttaagctgct cagacgagct 33600 ttaaatagtg gaaacacagc agcacgccga tcgccgccgc tatcaggccg attagaaaaa 33660 cggtggtcca ggggacgccc ttgggcctat cgcacgccgg cttttcggtc attacggtgc 33720 gcacgatgtt taggaactcc tcgaagtcct cgtccgagtt ggagaggaag gagccgaaga 33780 cgccggtgta cagtttgtcc atttaactact agatattaaa cggcgcttcc aactcctcgt 33840 cctcgaagcc cgcgccaggc tcgacgacgc ccaggccgcg cacgtcctgc tcctcgttga 33900 acgtggtctg agtctcgctc atgcgcacac acgtctgctc gccctcgaga ccgagcacgg 33960 tcagcgagca ctcgcgcggc atggtgatct tcttaaccgc gaaggtgact ttgccctcgc 34020 cgcccgagcg gtagaacacc accggcgcca ggatgagcgt cgccatctgc gcgtcgcggg 34080 ttgcgaggtt ttctatctct cgcgtcagcg gacatatctg cggctgggtg tcgtcgtcgc 34140 tggtgaactc caggagagcg ccggtcaggc ggttgagata cagacatccg gacttaaagg 34200 tgttgtcgat ggccgtttcg gtgttgaagt tgcgcagcga cggcggaacg cgagcgccgg 34260 ttttgatgtt gtcgtatatg ttctccagca gctggtagag cagcggactg gcgctcacgg 34320 gcttgaggcg accgaagtac ccgctgtcgt tctgccgctg catgtcggtc ttcttgctcg 34380 ggtagatctt aaactcgccc ttcacgacga tgagcggcga gacgagcttg gatgctagac 34440 tttcgacgag acacacgttg atgttggagc agctcgggta ctgcgacgga gttagagtca 34500 cggcctcgat gaccttggtt tggctcgacg agagcgactt agcgaagttg atcgcgtcgg 34560 tgcacgacat cgcctggttc tcgccgaacc gcctggcgga cgctgcatcc tcctgctgag 34620 gagcgcggtt agacgcgacg gtggttttgg atacagcgcg tttcattatt gcggcgattt 34680 taaagtacgt gtatactttc agttttgtcg ccgagcgttc agcgcctgca tgcagaggaa 34740 gtacaggatg atggtgcacg ggatcgtggt cagcagcgat acgaagtcca tcactgtgag 34800 gacgcgcagc gccccgcgcg agcggatgcc cagcgagggc gcgccgcggc gcgcgatggt 34860 ggccccgttc gtcaccacta ccagcagcat taggatggtc gcgcccacgg cgacgcccag 34920 gtcccgcgac tccatttata gtacagtata gagcgaccgc gtcacgaact ctcggctggc 34980 caacacgcgt ccgtcgggcg ggtgtccgcc ggccttcccg cggaactccg ggacctcgaa 35040 gctggacttc gtcacgcggt acgtgtactt gccgcgccag accaggtttt ccttctggaa 35100 gacgccgtcc atggtcacgc ccgccatgaa ggcgtccttg acgatgacca gcaccgcgtc 35160 tagcttgcgc ccgttgatgt gcgtgacgaa gtccgtgccg ctgcggctcg cgcagcggat 35220 gtccacgccc gagggcaggt ccaccacgaa cacgaagcgc ttcggcgcgt agagcaccag 35280 gtccgaggac ggcgacgccg aaggcgccga ggggaactgc cggtggtcaa aagggtgcac 35340 cacgcccacg atggacgtga cgcggtcgtc cgggaactgc gtcgcggcgc cgccgccgcg 35400 gtgccgcgtg accgtgcttc tgcccacgtc gtcgcagacc acgtgcagct ccgacacgat 35460 cggcagcagc gtggccagca tgcggtcggt ctctgtgcgc gtcgcgcagc ggtacgcgat 35520 cccgcagtgc gcgtcctgcg tgcgcccgaa gaagagcacc agcacgctcg cgtcctggtc 35580 gaagggacac acggccatca cgcccaccgg cggcggcccg tggcctgcgt acgcggagga 35640 gaactcctgc acctcgacca cggcgtcctc gcgcgcctcg ccgggcacca tcgccgccgc 35700 cggccgcagc gcccgcacgg tctgcttaac cgcacgcgcg gcggaggccg cgctcggcgc 35760 gactacgcgc acggccgcgt gcgcgcccgg cggcggcgcg gttccggcca tccagcccac 35820 cggcgagaag aacacgtcgc agacgtgcac gcccgcggcc tgcagcgcgc gcgcgagcgc 35880 gcgcacggcc tcccactcct cgcgaaaggc gctcgcgacc gcgagcgcct tcagcaccgt 35940 gtccacggag ttgacgggct tctggaagag gttctcgttg ttgtagatga actcggggag 36000 ctccacgggc actgtgaaca gcctaatctc gtgcgcgccg ctgggcgtga gccgcgtcgc 36060 gggcttgcgc acgccggcgc cgatctgctt gaagaagtgg ttcatggcgc cgccggcttc 36120 tcgggctccg gcgggagcag actatttatt cgggaggtta tcctttccga aagcacctgc 36180 acggacttcc gcgtccagcg ctccatcttc atgtactcct tcatgccgtc gctgagcacc 36240 tcgacggcct ccagcttggg cgctgtcggg tcgaagagga tgctcttgag cagcgtcatc 36300 ttcttgtccg cgaggaagcg gaagtaagtg tagatgcagc gcagcgcgcg gaagttctcc 36360 gggtgcttga tggtgcacag gatcatgaag atgcaggtga acatgccgca ctcggactcc 36420 atgagctggt tgacctcgag gttgatgcag ccgcgccgcg ccttgaagtt gtccacgaag 36480 aagcgcatga gcacgtccac gtcgcagttg cggttgtcca ggtccgcggt ctcggcgttc 36540 acgttgaagc cgtccgagaa ggaggtagaag tagaagtact tgcaggggtg gaactccgag 36600 gggctgttgc cgccggagtc gtagaaggac acgagccgcg agacggtgtc gaagatgcag 36660 cacttccagt ggaacatgta gcagaagccg aacatcacgt agcgccgccc ggcgcgctcg 36720 atcttgtcct tgagcgtgag gctgaccatg ttgcagcgga agcggtccgc cttttcgtgg 36780 atggccgcgc cgttgaggaa gttcaggttg aactggccca ggtacgcgac ctcggtgccg 36840 aacgcgaagg gcgccaccag actctggatg ctcacgttgc tcatccaggc gctgcggtcg 36900 ggctttatgg cgatgggcac taccttggtg ttcacgcccg tgctgacgcc cgcgcgcgcg 36960 aggtcgtcca cgttcagcgg catctgcgag aagtccacgg cctcggacac cttctcgcgc 37020 aacgagggct tgaagaagaa gcccagcggg accttccact ccagcgcgat cgcctcgcgg 37080 aagccgtagc gacccttgag gctggccagc aacgcggtct tctgcgcgac ctcgtccttc 37140 tcggtgtccg gcggcgcggc gtcgatgagc ccgcgcttcg cgaagtccag cagcgccgcc 37200 agcgggatgc acgagacgcg accggccgtc gcggattcgt cgaagcgccg caccacgtac 37260 ccgttgcagt tggtcttgaa gttggacacg tccaggtgcg cgctgagccc caccaccgag 37320 tagatgtggc acagaaggtt ggtgaacccc agctccggga ttttgctcac cactaaatcc 37380 gtgtacttgt ccatttatca tggagaatca tctgccggac atgctgatgt ttcccaactg 37440 cgtttctgtg tttccctttg agtactcgct ggaggacgtg ttccgcctcc ccgaggagcg 37500 acggcgcgcg ttcgccatgg ccgtgttccc gctctccaag caccgctgga ggggcgcgcg 37560 gctccagcgc gacgagcgaa gcgtgtggct cagcgtcgag gaggaccgcg ggcgcgcgct 37620 ggacgagcgg aactgctcct ggctctcgga cgtggccgcg cgcatggtcg acgacgaggg 37680 ccgcgcggtc acgcccgagg cgtacgcctt catgcgcgcc gcgcccggcg cgcgcgtcgc 37740 cgagctcgcc gcggacgcgg gcgtgctagc gggccttgtc gccggcggca acgcgctgcg 37800 cgtcttctcc tcggagtcca cgcaggcgcg cgagggctgg aaggcgcgca gcgtgggcgt 37860 gctcggcaac gcggcgccgc tggcgcccgt gccgctggca tcgctgcgtc cggaagtgca 37920 gcgcgagctc ttcgccgcct ggatcggccg ccgccccgtg gtgctcacgg gcggcacggg 37980 cgtggggaag acctcgcagg ttcccaagct gctgatgtgg ttcaactacc tcttcggcgg 38040 cttcgagcgc ctggacgccg tccgcgagtt cgcggagcgc ccgctcgtgc tctcgctgcc 38100 gcgcgtcacg ctggtgcgcg cgcacaccgc gacctacctc gcctcgctgg gcttcggctc 38160 ggccgacggc tccccggtct cgccgcggta cggcgccatc ccggacgccg agcggaacac 38220 ggccccgcgc gcctacgggc tcgtggtggc cactcaccgg ctcacactga ctgccatccg 38280 ccgctacgac acggtcgtag tggacgagat ccacgagcac gaccagatgg gcgacatcgt 38340 ggtcgcggtc gcgcggaaac tgggctcgaa catgcgatcg ctggtgctta tgacggccac 38400 gctcgaggac gaccgcgcgc gcctggagga gttcctggac cggcccgcct ttgtgcacat 38460 agagggcgac acgctcttcc ccatccgcga ggtctacgtg aagaacacgc aacagccgcc 38520 gctctcgcgc aagtacgcgg aggcggagct gcagaacgtg gcgcaggcgc tgggcacctt 38580 cgtccccgag cagggaaagt gcggcatcct cttcgtagcc acggtggcgc agtgcgcgct 38640 cttcgcggag accatcgagg ccaagcaccc cgggctgctg gtgcgcgtgg tgcacggaaa 38700 ggtgccctcc gtggccgcgg tgctcgagga ggtatacgcc gcggaccggc ccgcggtgct 38760 ggtttccacg ccgtacctgg agtccagcgt gaccgtgcgc accgccacgc acgtctacga 38820 cactgggcgc gtgtacgtgc ccgagccctt cggcggccgc gagaccttcg tctccaagtc 38880 catgtacacg cagcgcaagg gccgcgtggg ccgcgtggcg cccggcacct acgtgcgctt 38940 cttcgacacg cggctcgcgc tgccgctgaa gcgcatcgac tccgagttcc tgcacccgta 39000 cgtgctttac gcgcgcatct tcgggctaac gctgcccgac gacctgctcg tgcagcccag 39060 cgacctcgcg ctgctgcgcc gcaccgagga gtacgtcgac ggcttcggca tcagcctctc 39120 gcgctggacg cagctgctgg accggcacta catgcacatg gtcgagtacg cgaaggtgta 39180 cgtgcgcggc gggcgcctcg ccgccgcgct ggacgccttc gagcgcaccg gcgtgatgac 39240 gcacgaggcc accgaggcca tccgcgccgt ggacatgctc gcggccgtcc taaacgtgcg 39300 caagtccaag gaccgctacc gcgcggagtg caaggtgctc ttcgggccct tcgcgggcaa 39360 aaagttcgtg gtcgccgggc ggcgtccgcc cggctcgcac gtgctcatgg tcacagaccg 39420 cgtcttcatc gaggccgagc ccccattctg aggaccacct tcttggagac gcccgagaag 39480 tcgtcggcga cgccgcggcg cgccaccaca aggcagtacg aggtcacgtg cgggcagcgc 39540 gcgatgcagc ggaaggcttc ctcctgcgac agcgagaagg cgaacacgta gaaggtgtgc 39600 ggggacttca gcggcgtgtg gtccatcgag tagatgacac cgagcttctt catgcgccac 39660 ataagcgcgt tgatgtggtc ggcgcgcagc gcgcggccct tgagcacgcc gcagacgaag 39720 ctcgagcagg ccacgacgtc gtagcgcgtg ttcctgccga agaccaggtg cggcgcgccg 39780 gcggcgcgcc gcgcggccgc gcgattctcc acgatgtcct ctatggagcg ctcgctcgca 39840 aagaagtcca ggaacatgta ctggtaggcc acggccgggc gcgacttgct gaacttcatg 39900 aaggcgtccg agtccatgat ggcgtccatg tcctcagcgg cgagccggtg ctgcagccgg 39960 atgccctcga aggtgtgggaa gagccgcgcg tccgcgtgca tggacagcgc gagagtgacg 40020 aagttgagaa ggtccgcgtc gccaaagcgc acgagcacgt taccgggcgt gcgcgtcttg 40080 cgcatgagcc gcgcgggcgc gccgtcgttg tggctgcggc ggcgcatttt gtcgccgggg 40140 gactcgggcg gcaggtcgat catgaccagc cggtgccgct gcgcgtcctc ggcgttgaag 40200 atcgaggacg tgaagcccgg gtacagcacc acgcagtcgc gctccgagat ggcgtgcagc 40260 acgtcgcgct tgagcccggc caccagccgc tccgcgttct cgacgaagta gttctcgtag 40320 tccaggatgt cgtgcgccat ccaggggaag ttcaggtacg cgttcatggc gtagtcctcg 40380 gcgtcgaagc agatgcgcgt gtctggcgtc gccgcgatcg gaaggtcctt gatgccgcgg 40440 agcagcccgt cgtagtcgga ctcgtccacg aaggagagca ccacaaagag gtcctcgccc 40500 acggtttcgt agtcgaagag gtggtaaagc tctcttagcg ccagcacggc gagcgcgttg 40560 tccagcgagg cgtgcacgcg cgccaggatg ctgtagaagg gcgtggccat catcacggcc 40620 ttgccgccct cgcaggcaac ggcgcgcggg aaaatgacct ccggcgtgcg cggcagccgc 40680 ccgaacgtcg cgttcagcag cgcgaccgtg gccgcgtcgc tctggcgcag gaacactacc 40740 accgaggggc ccgagatgct gagcatgcgc tcgcgcatgc gcgctggcag gtccggcgtg 40800 gtcacgaggt ccgcgaagcg gccgccgttg tagaggtcgc cgccgccgag gaaggtgagc 40860 acgtcgaagc agtgcagcac ctcgttgcgg aagtagtact cgttctcgag ctccttggcg 40920 tacgcgcgta tgtccacgtt ctcgaagttt gttcgcagac cgccgccgtc gaagaaccag 40980 gacgcgagct cgcggacggc gtccgcgggc ctgttgcggc ggctcttgca ccagaagctc 41040 atgtagttgc gcgaggtgga ggcgttcgcc aggaagaagc ggtggtcgaa ggagatgagc 41100 acatgctcga gcaggtgcgc gagccccagg accgcgccca cgtcgcgccc aaaaccgaag 41160 tttgatatcc ccaggtagac gtcccgtttc atagacggcc tcaggaacac cctgacgccg 41220 ttttccaaca ctatcattct ccggtattta cttacccaaa agtagtatgg ggagaagtgt 41280 ttgaacgtcc cctcgccttt ttaaatcaaa agtagacttc tcgcgcccgt gcgccaccgt 41340 cacgcgcgcg cggcgcgagt ccataccggc gatcaccgcg ctgctctgcg gtgcgtccgg 41400 ccgcgggaag agcacggtct cggagatccc gtccagctgc gcgtcggtgc gctgccgcca 41460 cgcgtgcgcg tccgcgagct cgcgcacggc cagctgcatc ttgttcgtcg gcaggaacgt 41520 gaacacgtac gccgccgcca ggaaggctgc gaagagcacg aactcaaccg cccatgacat 41580 ttagggagct gattttgttc cacgcggcga cgcacgtcgt gacgggcgac cccgaggcgc 41640 cgcggcgcgc ggcctcgctg tgccgcggct tcggcgtgga cttccgcgcg attcacgcgg 41700 agttcgcgcg gcggtacccg cgcaccgcgg ccgccgtgga gcgcgcgcag ccgctgcccg 41760 aagtcgatgc cgcctttccg ccggacgcgc gccggcaagt cgtgcggctg cgcctcgagg 41820 ctgcggcgct ggtcgtcaag gagtcgcgtg cgctatcggc ctccatgcgc ggcgtggcgg 41880 tggtcgacgg ctgctgcgtg cgcgtgtgcc gcgccaacga cgagctgcta gagttcctcg 41940 cgcggcgcta cgaccccgcg gtctaccgct acgcggaggt gccctcgccg agcgtgcgcc 42000 cgggctcgaa agtcttcgcg tgcgcgggcc gcagcgtcac ctttgcggcc gcgcaccgga 42060 gccgcatcac ggccaaccgc ccgctgcgcg tggtcgtgac cgaggcctgt gtggacggcg 42120 tgctcgcgcg cggcgccgcg gaggtcttcg accgcggctc cggcgtgctg ccccgcgcgc 42180 tgcgcgagat cttctaccgc ctcgacgagg acggctgtcc cacgggccag acgccaggct 42240 tcgcggacag tatggcgtcg cgcagctgat ctatgtccac ctttttctcg tcgatctgcg 42300 ccacgaccac gaaactgcga atgtccacag cggccatggt cttggccacc gggtcgtact 42360 tgaggagcag cacgtactcg ttgccgaagt gctcggtgac ctcggtgatg agccggtaca 42420 cgcccatgcc gagcacgttc accgcaccgt ccttggcgaa gagcgagagg atgttcacgc 42480 acttcagctc catctcgccc tcgaggcgcg cgagcatgcg ccgggtgacc tcgcatactg 42540 aacaaagagg cttacctagt aagataagcg ttagcttagc cgcggtcggt gacgcgtcgg 42600 aggccattta tggggatcaa aaacttaaag gcgttgctgc tcagccacgg cgcgctgacc 42660 ccgcacgagc cgggcggcga cgagcgcttc cctgccgtgt tcgtggacgg cttcagcgtc 42720 atgatgacca tggcgtactc gtgcgcggac gaagacgagt tccgcgcggc cgtcgaggag 42780 cgcgtgcagc actggatgag cgtgtccgag agcgggcgga tcgtggtctt cctcgaccgc 42840 ggcgagattc cgatcaagca gccgctgcgc gaccagcgcc gcaaagccac gcgcgaccgc 42900 gccgcgcgcc accgcgagtt catcgccgcc gcggaggcag acgcggcggc agaggccgtt 42960 ggcgcccgcg aggacaaaca ggaggacgag cacgcggagt tcgccgagga gatccgcgct 43020 gagaagcagc taaagctgca gcgcatccgc ttccagctca gcatcgccaa ccacgaggtc 43080 gttaagtcgc tgatagagtc cacgctcgcg cgcgctggcg atgccgtgga gatcgtcttc 43140 tgcgacggcg tcgacgcgga gatggtcatg tgcgcgcgcg gacgcgccga ggccgagcgt 43200 cgcgggcgct ggccgctgct cgtgaccacg gaccaggacg cgcttttgtt cacgtccacc 43260 gatcgcgacg agaagatagt gagcaccgtc tccgcctgct acgcgttcag gcccaccgag 43320 acgaccgagt acctgtgcaa acttgcggcg ctggccaacg gctgcgactt cttccccggg 43380 ctcggcggca tatgcgtgag tgtggagtcg ctgcgccgcg ccacgctttt cccggaattc 43440 tccgtgcgca acgccgccgt gagtctgtgc acgcggccca tgcggctgtc cacgcaggac 43500 gcgctggagc cagaggccgc cgccgaggtc gtggaattca tcaggcggta cgccgccggc 43560 gacgagcgca tctaccgcga ggtgccgccc ggcgcgtgct gcggacgcgc gtttgtgcgc 43620 ggagcgctcg cggccgagtg ggccgacgcg ctgccggcgg ccacgggtct gagcgtggtc 43680 gcggacatga tcgcgtgtct gcccgcgcgg cgggaccccg cgcccgagga ggtagagcgg 43740 ctgctggcgc tggaggcgcg cgcgcgaggc gcgcgcgtca cggatgcgat gctcgcgcag 43800 actgcgcagc tgctgggtta cggcgcgagt gcgggcgccg acggcgcctc cgccttcgcg 43860 gtctcgggcg ccaagggcct gatgtgtcgc ctgcgcggca cggccatgtt cttcaacgcg 43920 gagtacgtgg aaattgaaag cgaacccaga ctgttaaagc tgcggtagca tggtgttccc 43980 gatcgtgtgc tcaacgtgcg gccgcgacct gtcgcacgag cggtttctgc tcatcgtgcg 44040 acagcggccg ctaaaggttg ttttgcggac ggtgcgcaac gtctgctgcc gtataaagtt 44100 gtctacacaa atagagccgc accggaacct gacggtgctg cccatgctcg acataagctg 44160 atttttcttt tccgctcgta tgcgcgagtt cggactcgcg gcgcgcatgg cccgcgccat 44220 cgaggacgtg tgtccgcgcg gcgcggtgat attcgtatcc agcgccgcgt ccatgaccga 44280 ctgcctgaac ccgtcggtgt tcaagcacgc ggcgatatac gcggggcgcg tggaccgcgc 44340 gccgctgccg ccgccctcgc cggtcccggc ggaggccgtg acggagccct gtgcgataga 44400 cgccatagcg ccttacggcg cgcgcgtggt cctgctctcg gagctgctgc ggagctgcgt 44460 ggccgttcag gcctaccgcc tggcagtccc cggcgccctc gcgctcatga acctcgcggc 44520 cgacgcggcc ttcgagctcg tgggcacgcc ctacggcttt aacagcgacc gaacgtactg 44580 cttcaagctc gttgccgact gctttgctag cgtgggcgtg acaacgaaga ccaggcgcat 44640 catgggtcgc gacgtcgtgc tcagccagga cttcctggag agcggcatgt ggaccaaggt 44700 gctggactcc gccgcggagc cgccgtggct ggtctagaac agcggcggcg cgcgggtccc 44760 gagcacgggc cgcgccacct gcagccgctg ctgcagcgcg cggcactgcg cctcggcgtc 44820 ggccgtctcg gcggggtcga cgggcgtcgg agttgcggag gtggtcctga acggctgcgt 44880 gttcaccgag acgcggatgc gctccttgca ggagcgctgc tcgatgcagt tggccagcat 44940 cttcatcacg tgcaggtact ccagcaacac gaacttttcg agggtgatgc cgtcgaaggg 45000 cgacgacccc accacgccca gcgggctgga caccgcgccg tcgagcacct cgccgcggga 45060 ctccttgcgc gcgcgctcga gcaggtcctc tgtccgagcc accacactgc cgaagtcggc 45120 ggccgcgggg gcgggaacag gcgcagcagc gctgtccgcg tccgccggca tctcctcgat 45180 cttgagaccg gccgcgaact ccgaggccgc gtgcacgggc gaggcgccgc gccgcaccat 45240 gaagtcgcac agacgcgata gcgcggagga gcgcaccggc atgtcgagca ggcgctcggc 45300 ctccatctcg gcgaccgagt cggcgcacgc gtccggcgcg cccgcccgca cgagctcgtc 45360 gcagcacccc gcctccttca tgagcgcggg catgagcttg tactgcgcca tgttcaccag 45420 cccgtacttg agctcgagca ggtccgcgag ctcggaggcc atgggtcggt ttttggtgta 45480 gatgacgcgc tccacggcct ccgccatgtc cacggcctgc atgagctcgc cgacgagcac 45540 gctggccacg agcgtggcca gcgtgacgcg cacggtgggc acgcagaccg cgaagaagga 45600 ggtggagtgg gtgaagcgca tgagcgcgcc gtgcagacgc gcgaggtccg cgctgttgcc 45660 cgcgtgcacg aagcgccggc gcagccgcgc cagcgcctcc acaaggtcct ctcgcgtggt 45720 cacgcgcacg ttcgcgatgc acaggtcgtg gatcgcgttg gcgatctgcg cgcggcgctg 45780 cggcgagctg ccgggcagca gccgcgcctt ggcctcgacg tcgacggtgc tcgagagaca 45840 gccgcaggcg gcgccgcgga cgacgaactt caacaacgac tcgaacacgc gcgcgcccgc 45900 gcggggcgct tgcttggacg actccattta ctttaaataa tttacgagat caaaataaaa 45960 tgactctgcg catcaaactc gagaagctca agcagatcgt aacttacttc tcggagttca 46020 gcgaggaggt ctcggtgaac gtggacgtcg gcgatggcct catgtacata ttcgcggcgc 46080 tgggcgggtc cgtgaacatc tggaccatcg tgccgctcag cgcgagcgtg gtatacgacg 46140 gcgatgtcag ccgcgtgttc aacctgcccg tgctcaaggt gaaggcctgt ctgtgcagct 46200 tccaccccga ctcggtggtg agcctggagc ccgacctcga ggacaacgtg gtgcggctct 46260 cgagccacca cgtggtcagc gtggactgcg acaacgagcc cgtggcgcac cgcacgaaca 46320 ccgccatctg cctgggcatt aaccagcgca agtcctacgt gttcaacttc cggcgctacg 46380 aggagaagtg ctgcggccgc accatcgtca acctggacct gctgctgggg ttcatcaagt 46440 gcatccacca gtaccagtac atcacggtct gcttccgcga caagaagatg gtgctgcaca 46500 cgcccgggaa ggtggacaac ttcttccgcg agtactccat gaccgagtgg gcgcccgacc 46560 tcgagcgctt ctcgttcaag atccccatct cctccgtgaa caaactccgc ggcttcaaga 46620 agcgcgtggt catgttcgag tcgcgcgtgg tcatggacgc cgacgacaac atcatcggca 46680 tgctcttcac cgaccgcgtg ggcatgtacc gcgtgaacgt gttcatgtcc tttcaggacc 46740 ggtctctttc atgcgactaa atactcatgg gcgggtcggt gagcctgccc tcgcgggacc 46800 tgccgccgcc ggtgcgcacg ccggagatga acatcgtgcc cgagcgcgac ctcgcggaca 46860 cgatggcgcg cctctccacc gcagacccgc cgcagccgct gggcgtcggc gacgacgcgc 46920 gcatggccgt gctgaagacg accttccccg agttcgcgat atcgcggccc gcgacgggca 46980 tgctcgccgc gcagcgaatc aggtacgacg gcgacccgcg cgtctgctgc ggcgggttcg 47040 ggatctcgca ttactgggag aagggggcgc gccgatcgaa cgtcgcgttc gagggcgcgg 47100 cgctgcgcac ctgcgacccc acgcgcttcg acgcgggcgc gtgcgacgcg ctgctcttcc 47160 gcgagtgcgc cgccggcggc gtcgacgcgg acttctgcgc gcactggatc aacgcggccg 47220 tgacgcggcg cacggaccga cagtcgcgcg cgcggctgaa cgacatgttc gtgcgcgatt 47280 gccaaaacga cgccgcccgg cctcactgcg tggcctggat ccgcgcgatg cgaagcgcgc 47340 gcgcgacggc ggacgacggt ctaatagacg ccgtgctctc ggtgcagagt cccgagttca 47400 agggcaagca catgcgctgc agctacccct cgccggccac tctcgccatg gccgcgaacg 47460 tggacgagcc gcgcgagtgc tgggaccccg agtgcgtggc cgggaacgtg gacttcatgc 47520 taagcgataa ctacacgaac ctgggcttgt gtcggctctc gcgctgctcc atcggcgtca 47580 cacacctgcg gattgacgcg cgttcgcggc tgcgcatgcg gtgcgccggc gcgcttgccg 47640 ggctcacgaa ggcgcccgtg aaccagactg tcgtcgtcgg cgacaacctc gcgcgcgcct 47700 tcgagccgcg cgtggaaacg ctcagcgtgt tggcgctgtg cgtggtgtat ctgctaattg 47760 tctggctcta aatgggggcc gccgccagca ttcagaccac cgtgaccacc gtcagcgagc 47820 gcatccgcaa cgagctcgag cagagcgcga gcgctagcgc gaccgccgac tgcgacgtca 47880 ccatcgggag tctgattatc cgcaagaacc taggatgcag cgtttccgtc cggaacatgt 47940 gctcggccaa cgccggcgcg cagctggacg ccgtcatgaa ggccgtgagc agcaccttca 48000 acgacctctc gtcggaccag aaggcctacg tgcccgggct gctcacggcc gcgctcaaca 48060 tccagaccac ggtgaacacc gccgtcaagg acttcgagac gtacatgaag cagacctgca 48120 cggcggacgc ggtcgttcac aacaaaatca agatccaaaa catcgtcatg gaagagtgcg 48180 cctctctgcc agggagtccg gccacgcacc tggatttcgt gaacaccggc acggccgtgg 48240 gcaactgcgg cgtgaaggcc gtgatggacg tgctcgcgaa ggccagcacc accgtgcgca 48300 acgaccagga ggccggcaag ggctaccaga ccatcatcat cgcgatcgtg gtcgccatcc 48360 tggcggccat cttcgcctgg tacgcgcggc acatgctatt catgtccacc tccgacaaaa 48420 tcaagctcga gctcgccaag aagcccgtgg tgcactggac cacctacctg gacaccttct 48480 ttacggaatt tccgccgtcc gtctagatac gcgcaacatt gaaacattat atccacctct 48540 caaacggcgg tatggtccga cgcgtcctcc tcgagcgcgt ggacggcatc gtcgagcact 48600 cgcgcgcaga ccgacgctac ttggaggcca ttcagcgaca cctcgagggg tctacgcccg 48660 ggctgcggca gatgtggcgc ttcctctacg acctgctgct gacggtgttc gtcgtcatgt 48720 acatcgtctt ccgcctaatc gtgcgcaacc ccggcatctg cgccatcctc gcgctcgcgg 48780 ccgcggtgta ctacctgttt ttgtgtctct ttagcatgga ctgatggcga tcacagacag 48840 accatcgccc gcgcgcgcgt gaccagctcc ggcgccgcga agacgtcctg caccgggaag 48900 tcgtcgatct cgaacacgga gccgtccgcg gaccagatca cgcgcacgtt gtcgctcacc 48960 gagacctcgg tcagcgtcac gcccagcaca accgcgtcgt tggtgctcac cagcaccagc 49020 gcgccgggct ccgcgcgccg gtgcagcggc ggccccgaga ctgagcgccg ctgcacgcgg 49080 aacatgtccg cgaactgctt cgagagcaag tccaggtggt tgcggatgat ccactcgaag 49140 aagtacgcgc aaccgccgcc gccgcacagg aagcgcgaac ccgcgggcat cagcagccgc 49200 acaacgtcca tgtagcaggc ctgcggcagg ctcgcgcggt acagccgcgt cttcggcgag 49260 agcaccacca ggctggaggt gctcatctgg aagaccagct ggctaacgga gacggtgagc 49320 gtgcacgcgg gcacggaaac cacgtccagg cagatgtcgt ccagaaagat gctccgctgg 49380 tagaggtggt acaggatggc cacgatctga aaggccgtgg cgtcgctgat ggcgcagggg 49440 cggtcggcgc agcgcatctg cgcgcaggac cagcccccga aggactcgaa gcagacggtg 49500 agcatgcccg tgctcggaca gtgtggcgag cgccgacaca ccggaaagcc cacggccttg 49560 cggcagcgca ccatggtcga gagctctatc cagcagcctg cctcctcctc gcccatgccc 49620 atggctaccg gcgtgaaggc cgtgacgtcg tcgcagatgc gccgctccag aaaccccacg 49680 cccgaggagg ggtgcgcggc cggcggcgag gtgatgcgcg ccgggacgcg gctcggagcg 49740 ggctcgggag gcgagctgcg ctcgacccgg gcagtcgccg ccggccgcga tgccctgcgc 49800 gcgggcgcgc gctcgcgcaa cttgtttgac ttgctggcct cgtcgctagc gtcatcgaag 49860 cggtcgttcc tgtcgccgcg gacgtccgcc tcgtcgcccg tcggctgcgc ggcgggcgac 49920 gtgccgtccc gcgtacggcc cgcgttcggc gcgaatgtca cgcgccggtg cacgtacggc 49980 tccgtagagc ccgtgggggc gccgcgcccg cgcccgcggc ggaaggcctg ccgggacgcg 50040 ccgaagcggg cgaactcccc cttcgcccgg cccctttttt cttccatgat atttatcaca 50100 aaaaaaactt ctctaaatga ccaatctgct ttcgttggtc gacccggagg acctggcctt 50160 ctgcgccggg ttcccgtcct tcgacgagac catgctcgtg atcgcggggg cgcgagtgcg 50220 cttcccacgc tcgctgctct cgctcttcaa cgtggtgccg cgcaccatga cgcgctacga 50280 aaccgagctc gtgggcaccg agatggtggt gggcgccgtg ttcaccaccg cgtacaacgt 50340 ccgccgcaac ctaggcctcg gcgaggagcc cgtgaccatg cgcgacatcg agaagtactt 50400 cctggactcc gagaacgagg tgctcacgct catcgtgcac aacaccgact tttccgccat 50460 gagcggcgtg cgccggcgcg gcggccggcg catcgccaac cccgtcatct tccgcagcgg 50520 gtccacgccg ctgctcatcg tgatggagtc gcgcaagaag accaacatct accgcgagcg 50580 caccgcggag caggccaacg cctcctacag ggaggtcggc tcctcgctcg cgctggtcac 50640 tcggtacgcg ggtctgcagc tggttgacgt gcacacgccc agctccgtgc taacggtctc 50700 cgccgtctac ggcttcaccg aggacaaggg gctcaagaag ctgggctccg acaaggagct 50760 cgcggactac cagtccacgc cgctcaccga ccccatccgg ctcagcgact tctccaatat 50820 attcgacggc gtcaagaaga gcatccagct cacgaacgtg cccgtgccct ccaccggcgc 50880 cgaggccgcg ccgtaggctt tcatgcgcga taaatcggat ggcggcgccg acgacgcccg 50940 cggtgcacct cacgccggtg ttcgtggagc ctacgatcgc gcactcgctg ctgcgcgcag 51000 agtcctacct cgcgatcgcg gtccttgagc tcgtgctcgc gctcgcgctc gcgctcgtct 51060 tcttccgcga cgagctaggc tcgctattcc gctgcgcgcc gcgagcgcct tcgccgctgg 51120 acgcgtacct gcaggcgagc ctcgtctgcg acggcgacgc gctgctgatc gagctgcccg 51180 agggccgggt gccggcgctc gcgctggacg ggcggcccgt cgcgttcccg gggtgcgaga 51240 gccttttgta ccgcataaat ggaccacgaa aagtacgtct tgtcgatgtt cttggaggaa 51300 gataactcct tcttctcgtt cgtcgccgcg ctgtccgatg acgaggcgct cggcgccgtg 51360 cagtccgctg ccgccctcct ggacttcctg ctctccgtgg tggtccgcgg caaggagaag 51420 ctcgccgccg cggggcacca ctacgactcc atcgcggacg gacgcgcgcg cgccgcgttc 51480 gagttccgag acctgcgcga gctggcgcag ctcttcgacc ggcggccctg cggcgtccag 51540 gaccgcgtgc gtgtgcgcga cgggcccgcg cgcgccttcg tggacgcggc actggggctc 51600 atgcgcgagc gaggcttcga cggcacgcag gccgcggagc gcgcgcgcta catcgcgccg 51660 aacgatctgc ccgcgctggg ggcaatatcg gccacgctct cgccgggtct ataacgtaaa 51720 aaatattagt aaaattctga aggtccgtgt gtttcgcggg cggccaacaa accagtcgct 51780 taaatggagg gggtggaaat ggacaagccg ctcctctact tcgacgagat cgcgggcgcg 51840 cgcgactacg acgcggcctt cgcggagaag cacgagccgc ccaagatccc cggccgcgga 51900 cagatgaagc tgctggtctg cgagctcgtg tttctcaacc ggctgcacct gcacggcatg 51960 ctcgacggca gcgtcatcgt gtacgtggggc tccgcgcccg gacggcacat ctgctgcctg 52020 cactcgcact tccaggagct cggcgtctcg cttaagtggg tgctcattga cgggcgcaag 52080 cacgacccct gtctctcggg gctgcggaac gtgaccacgg tgacgcgatt cgcggacgag 52140 gcctacctcc gcgagctgcg cggcgagctg cggcgcgcca agatcgtgct catttcggac 52200 atccgctcca accgcgtgga cacagagccc accaccgcgg acctgctgcg cgactacgcg 52260 ctccagaaca ccatggtgag cgtgctcaag cccgtggcct ccagcctgaa gtggcgctgc 52320 cccttcccgg actcctggga gaaggacttc tacgtgccct gcggcaagga gatgctgcag 52380 ccgttcgcgc cgccgttctc cgcggagatg cggctgctca ccgtgtactc ggagacgcgc 52440 ccgaagctgc gtctgatcac gctcagcgac gcggtcaact atgaaaagag gatgttctac 52500 ctcaatagcg tggtccgcca gcgcgtaatt ctgaactttg actatcccaa ccaggagtac 52560 gacttctttc acatgttctg tctgctctcg tcggtggtgt gctcgtgcga atttaaatcg 52620 cccaaagaga aggtgctgag cctgcagaac cgcttcttcc gcttcctgcg catcccgccc 52680 tccatcacgc tcgggctgcg ccggcacgat gaaccgccac aacacgcggt acctggccaa 52740 gatcctctgc ctaaaggccg cggtaagaag cgaccccttc gcggtggtaa gtagggacac 52800 cgtgcgcatg tacgacatcg aggtcgagta cggcgacctc gtgacggtgg tcaccgtcac 52860 gcacaaactc gagaccagcc gcaccgtctt ccaggtcttc aacgagacct ctgtcgcgta 52920 ctcgccgctg ccggacgact acggcgagcc catcgtgctc accacgtaca tgcagcgcga 52980 gcacaccaag ttcccgctct ccatgctcta catcgacgtg gtcgcctcgg acatgttccc 53040 cacgtttaag cgccccaccg aggaggaggc cgcggtggtc gcggccatgc agcgcgtggg 53100 cgggcgccgc gagcccgtgc tcaagctccc gcgcatgctg gacaccgagc tcgtgtgcaa 53160 gatactgcac ctgcccgagc acccgctgcg cgtggtgcgc ttcctgcgcc gaaacatgtt 53220 cacgggcgtg gaggtcgccg accgctcggt gtccgtggtc ctcgactgac gaagggcagc 53280 acggtcagcg aggccgccgc caccaagcac agcggcagcc acgcgcgcgg gtccgccacg 53340 ggcacgaaga cgtgctggtt caggtacttc gcctggaagc gctccgcggt ggagtccacc 53400 ttggacccgc aggcgttggt gaggcgcacg accgcgtccg cgacgcgcac gtccccgagc 53460 gatatcacgc agtcagagac gttgcacccg gcgatgtttt tcttcagcgc gcgcggcagc 53520 agcgcgtccg cgcgcttgca gggcgcgtac cagcagtagt agggcaggcg cgtgtcgcgg 53580 ccggtgtcga ccacggcctg gctgggcttg aggcacgcgc agcgctcgtc gtccgggtgc 53640 gcgtcgcaga aggcgtaaat ctcctcgtcg ggcgcgtccg gcccgggcgc ggtcggcggc 53700 gccgcgcgac ggcggaagaa catctctgaa aaaatacttc gaccagaaaa cgaccaccga 53760 tcttatttca aagataaaaa tactattaat acgcactcgg agaatcatgt cggtggtggc 53820 gcgcgtgtcg tacagcctgt actcgcagag cgagataagc gccacggacg tggtcatcag 53880 ccagttgaag aacgacgagg acctgggcac ggtgaaggac ccgcgcctgg gcgcctcgga 53940 cgggtccata tgccgcacct gcgggctcac ggagatggag tgtttcgggc actggggcaa 54000 ggtgcgcatc tacgagtcct acatcgtgcg ccccgagtac atccccgagg tggtgcggct 54060 gctcaaccac ctctgcgtgc gctgcgggct gctgcgctcg cgcgacccgt acacgacgga 54120 cttggccgcg ctcagcgtgc acgagatgcg caagatgaag gaccggatga tgtccaagaa 54180 gaaggcctgc tggaacagca agtgtctgca gccgtaccag aagatcgtct tctccaagaa 54240 gaagatctgc ttcgtgaaca aggtggacga gatacccgtc cccaacgcgc tcatctacca 54300 gaagctgacc tccatccacc gcaagttctg gccgctgctg gaggtgttcc aggacccccgc 54360 gaacctgttc tacaaggagt acatgcccgt cccgccgctg ctcatccggc cggcgatcag 54420 cttctggata gacaacatcc ccaaggagac caacgagctc acctacctgc tgggcatgat 54480 cgtgaagtac tgctccatga acgccgagga gcaggtcatc cagcgcgccg tgatcgagta 54540 cgacaacatc aagatcatct cctcgaactc gagcagcatc aacctctcct acatcatcgc 54600 gggcaagagc aacatgctgc gcagcttcgt ggtcgcgcgg cgcaaggacc agaccgcgcg 54660 ctcggtcatc gggcccgact ccgcgctctc ggtgtgcgag gtcggcatcc ccgactacat 54720 ccggaacacg ctcacgcaga aggtgttcgt gaactacctc accagcaagc gcgtgcgcgc 54780 gctgttcgag gaccgcgcgg tcaagttcta cttcaacaag cggctgcgcc agctcacgcg 54840 catcaaggag ggcaagttca tcaaggacaa gatccacctg ctgcccggcg actgggtgga 54900 gatcccccatg tccgagggca cgaacgtgat attcggccgc cagccctcgc tgcaccgaca 54960 caacgtcata tcctcgaccg cgcgcgcctc gcccggctac accatcaaga tcccgcccgg 55020 gatcgcgaac tcgcagaacg cggacttcga cggcgacgag gagtgggccg tgctcgagca 55080 gaaccccaag tccgtgatcg agcagagcgt gctcatgtac ccggtgacta tcttcaagca 55140 cgacgcgcac ggcgcgccgg tgtacgggtc catccaggac gagatcgtgg ccgcgttctc 55200 gctgttccgg caccagaacc tctcgctgga cgaggtgctg aacctgctcg ggcgctacgg 55260 gcgagacttc gcgccggagc ctggccagaa gaccttctcg ggcgccgacg tcttccgatt 55320 catgataggc gcggacataa acttcaaggg cgtgctcgag aacgggcgcg tggtggcgcc 55380 gaacgtcgac agcgacctcg tggtggccat gcgcgcaacc tcgctagcgg ggctgatcgc 55440 ggactacgcc acgaacgtgg agggcgtgcg cttcgtggac atggcctcct acgtgtacaa 55500 gcggtacctg gccatctacg gcttcggcgt gaccttccgc gacctgcgcc cggacccgag 55560 tttggttcgc cggctgcacg cgctgaacac cgagaagata gagcagatca aggacgcgta 55620 ctcgcggtac ctgcaggacg tcgcggacgg gaagctggtg ccgatggcgc ccgcggacga 55680 ggccgacgcg ctggactcgc tgctggccaa cctgaccaac ctcaacgtgc gcgagatcaa 55740 cgagtacatg cgcgagacgc tggagcgcaa ccccgataac agcctgctaa agatggcgcg 55800 cgccgggtac aaggtcaacc ccacagagct catgtacctg ctgggcacct acgggcagca 55860 gcgcgtgaac ggcgccgtcg ccgagaccaa gatatacggg cgcgtgctcc cgtacgcgtt 55920 ccccgactcc gcggacccgg aggcgcgcgg ctacatcatc aactcgctca tgaacggtct 55980 ctccggctcg cagttctact tcgcgatgct ggtggcgcgc tcgcagtcca cggacatcgt 56040 ctgcgagacc tcgcgcacgg gcacgctcgc gcgcaaggtc atcaagaaga tggaggacac 56100 ggtcgtggac gggtacggac agatcgtgag cggctcggta ctgctcaagt acgcggccaa 56160 ctacgcgaag atcccggggt ccaccaccaa gcccgtggag ctgctcttcc cgcacgagag 56220 catgacctgg ttcctggaga taagcgcgct ctggacgaag atccggcacg ggttcgtgcg 56280 catgcaccgg cagcgcctgg ccaccaagat cctggcgccg ttcaacttcc tggtcttcgt 56340 gaaaccggcg ccctcggagg cggaggcgct ctccgcgcgg gacctgtacc acatgatcca 56400 gcgcgtgatg aacgacgtgc gcgagaagta cttcttctcg ctggcgaacg tggacttcat 56460 ggaggtacgtc ttcctcacgc acctgaaccc ctcgcgcgtg cgcatcacgc gcgcgaccgc 56520 cgagctcatc ttccgcaagc tgtaccagaa gctgaacgcg ctgctcggcg gcggcacgcc 56580 cgtgggcatc atgtccgcgc aggtgctctg cgagaagttc acgcagcagg cgctctcgag 56640 cttccacacc accgagaaga gcggcgccgc gaaggtgaag ctgggcttca acgagttcag 56700 caacctcatc agcatgagcc gcaaccacac cgagatagtg gcgctgaccg cgccgagcgc 56760 ggacaagctg atgccgctga aggtaaactt cgagttcgtg tgtctgggcg agctcgtgcc 56820 cgagatcgag acccggccct cgggacggcc ctccgtgcac cgcgtggaca tcacggtgca 56880 ccgcctgcgc atcaagcgcg cgcacctgac cgaggtcctg gtggacacca tcatcgagcg 56940 cttcgtgtcc ttcaacgtgc tcgtgaagga gtggggcagc gacatgaccg tggagggcga 57000 ccgcgtcacg tacacgctgc tgctgcgctt cgtggagccg gagcagctca acttccacaa 57060 gttcatgctg gtgctgcccg gcgccgcgaa caagggcaag gtgagcaggt tcaagatccc 57120 gatcaccgag accacggtct acgacgactt cgacgccgcg cgcaaggcct accgcatgaa 57180 catcgagctc atgagtctga aggagctggg gatattcgac ctcgaggacg tgaacgtggt 57240 ccccggcatg tggaacacct tcgacatatt cggcatcgag gccgcgcgcg ggcacctctg 57300 cgagagcatg ctggacacct acggcacggg cttcgactac ctgtttccct cctgcgacct 57360 gctcgcgagc ctgctctgct ccgggtacga gcccgagtcc gtaaacaagt tcaagttctg 57420 gaacgcgagc gcgctgaaga aggccacctt cggcgacggc cgcgcgctgc tgaacgcggc 57480 gctgcacaac cgcaccgacg cggtcgcgga caacagcagc tgccacttct tcagcaagac 57540 gccctgcgtg ggcacgggct actacaagta cttcgtgaac gtggagatgt tcatgcgcat 57600 ggagcgcgag atccaggcgc gcgtggcggc gcgcaagatg gaggagatcg aggaggccgc 57660 cgaggaggag ttctaggcgc gacggcgcct tactttgcga ccgtgtcacg acgacacgac 57720 acggttagga cggcgagtcg cagacgaaca tttttatgag ctggtagcgg aagttggcgt 57780 tttccaggaa ggcgccgcgg aggtcccgga tctcgtagta ggttttgagg aagtacacga 57840 agcgcgcggg ctgcgtcata gtcgggttct ccgcaagccg cttgtgcatc acgtacccca 57900 tggcggcggc gccgctgcgg ttgacgccgg ccacgcagtg cacgagcgtg ggcttctgct 57960 cggcctcgag gcgcgccagc agcttcacga gcgcgggcat gatggaagcg atgttcgtcg 58020 tgtcgtcgtc tctcagcgga atgtggtacg ccgttatccc cgcgggcgtc gagtacttgg 58080 acatggtcat gttaaccaga cacttgaagt cgacgccgga gtccccccgc agcacggcgc 58140 gcgcgtcctc ggcgctgccc aagtacacgt ggtccgtgag ccgcgtcatg cccgagggca 58200 gggccagcgg cggccccgcg cgcgtgcacc gcagcaggag cctggcgtac cactcgctct 58260 tatcgcccat atttatttat atgatacaaa tggcagacgt cacaacactg acggccaacg 58320 gtctgaccct ggagttcgcg cgcgagcgcg ctctgcgcag tctgcgcgcc gcgcgcacct 58380 ccacgctggt gttcttcacg ctcacgctcg cggcctcgct gttcgtgctc tggctgcagc 58440 taaccgagtt tcccgtcttc gaggagctcg gcaagtacgc gcgcatcaag agcgcggtgc 58500 ggtcctggcg cccgctggtg gaggctaaga cagagatcga gtccgacctc ggccggcaga 58560 agaccgccga ccggcccgag ctcttcgagt tcaggtgcgt ggacttcggc aagttctacc 58620 tgccggtgag gtacagcccc acgaccttcc tgccgcaagc cgtgcgccgc ggcgcgggcg 58680 atggctggat ggtgcacaag gcggcggccg tggacctcgc cgcgcagcag ttctgcgagt 58740 ccgtgctgcg gcaccgcgcc aacaacgtca tcacatgcgg gtcagagatg atgcggctgg 58800 tgggctacag cggctacttc gaggacgacc actggtgcgc cgcgacgtcc ggcgtgctga 58860 cgtgaacgat cacacgatgg ccgtgaccag cagcccggcg atgaaccaca gcagccgcga 58920 gttcggcagc agcagcacga gcaccagcag gtacgccagg atgaagatgt cgaccacgtc 58980 cacgtcgaag agccccatga aggagaagag cggcgtggtg aggaagtaga tggcgccggg 59040 ccagaagcgc gccagccacg tggcgagcag cgaccacagg gagggcgcgc cgctgagccg 59100 cgtcttcacc tgtatgtagt actcggggta gaccacctgc tcggcgccgg agagcaccac 59160 gcgcgccaga gagagccgct tctccagcgt gaacacctcg gtgagcaggc cgctgcgcag 59220 ccctccctcc ttgatgatcg cgtcgtagag cttcttcatg ccgccgacgc tgatgatgta 59280 ggcgtctagc gagacgtcgt acccgccggg gtagaccatg agctcggggt cgccggtgcc 59340 ggggacgttg gtggccagcg cgccggtcat gtaggtctcc ttgagctgcg tcatgtacca 59400 gccgttcgcc ttcatcgcct cgatgagcgg cttcaccatc tcgggcttgc ggaaggtcat 59460 gtcgttgtcg accaccagga tgaagtcatc gtcggagtac ttggtgggga cagtgccggc 59520 cgatatgctc tcccagaggt tgaggtggtg cgctgcgcgg cgctgcatct ccttcggaca 59580 cgtggacttg cacatgtccg tgaagaagtg cgggtagtct ttggagtcca cgtctttcca 59640 ttccaccgcc ttgagcacgt ggtcgccctt ggggtgcggc gcgggaggag atggcttggg 59700 tgccggcgcg ggggccggtg cgggggctgg ggcaggagag ggagcaggcg cgggttgagg 59760 cttgggcggg tcgtcggcga ggcccaccag gtacggcagc gtggggaaca cctccttggt 59820 cccgcggcct tcggcaaccc cgattatgta ggccgtgatt tcgggtggat ccatttagtt 59880 attaaaatta atcatataca actcttttat ggcggctatg gattcggcta tccagtcctt 59940 gaccgagccc acgatgcccg ccaggaacag gaagaaggcg aactccaggt ccacgcggtt 60000 cagagagtcg ctgaagtaca cgaagacgtc gctgtccggg aagaagctgc gccggaacat 60060 gttgtacccg ttgaccttgt gcgcgacgtg ctccgcgctc agcagcgtct cgtcgaaggg 60120 gtacgggtcg ctgaagcgga acacgtacat ggccgggttt gcgtagtagt acttcatggt 60180 gtttgtgacg aagaggctcg ccagcgagat gatgattttt ttcttctcga tctcgatctt 60240 gatgtggtcc tcgaagcgct tcatgttgta ggcgttggtg tcgtgcacgc ggatgagcac 60300 gcgcgagtcc gacatgatgt cctggaactc cgcgcgcgcg tcggggctct cggcgggcgt 60360 ctccgcgggc cgcgccacct ccgcgcacac cgtcggccta gcgcgcggcg gcgtgcgcat 60420 gggccgcgcc cccacgcgct gcgaagcgaa aaactccacg gcgcgagcct cgcccgcgtc 60480 cgcgtacgac tccaccaggt agttgcggct gcgcgtggtg cggccgatgg tgttcagccg 60540 gtgcagctcc gcgaccagcc ggcggtagtg cgcctccagc tcctcgggca tgatggaggt 60600 gtacacctcg gtgagcagca tcacggtgtc gaagtcctcc ttgccgcaga cgcgcgtctt 60660 cacgaggaag tggtgcacag ccgtcgcgat agagagccgc agcgtggact cggtgacctc 60720 gacgctggcg tccttggtct tcttcgcgct ccgcgaggcc atgaacgaga cgaggaagtc 60780 cgcgctgctg ttgagcacga tgaccagcgc gacgatgaag ttgaggttca gcgtcttcgc 60840 ggactggaac agctcggtgg ccgacgcgtg cacgtcgagc aggttcgcgg agagccgcag 60900 gaagaacacg ccgcgcttga tctcggccgc gaagcgacgt tcgtactcct gccggcgcgc 60960 gttgatcgcg atgaggaagt tcaggatgag ccggttgatg ttgtacttca cggcccaggt 61020 ctgcgtcttc atgatggtgt cgaaggacat cacgatgttg aagatgaagc gctggctgtg 61080 cgagaagtag ctgtagggct cgctgaggaa gatggacttg ttggtcgcgg gcaccaccac 61140 gcccgcgcgc gcgccggacg cgtcggtgtt caggtccggg atgttcatgc cgcagatgcg 61200 gcagtaggcc atgccgtcct caaagtacac gaactcctcc acgaactcgt tgatcttggc 61260 gaagtagtcc acgtccacgc gcatcgcgac cgcgagccgg atctggtgct cgcagggcgg 61320 cgactcgaag cgcaccccct cgccccagcc cggcggctcg cgcacgacca gcgcggtgcg 61380 cgaggccggg cggaacttgg cgtcgcgcgc gttgagcagc gccgggaaga ggtcgcagag 61440 gtgccggctc gagaggaaca cgtacttgta cagcagccgg cgcgcgtccg cggccatggc 61500 gtccacgaag gcgcggcccc actccgcgac cgcgggctgc tcctccgcaa agttgttcgg 61560 gtagaccttg tccgtggccg cgaggaacac cttcttcacg tcgaggaagt cgcggatcac 61620 gatggggacg cgcgcgccgt cgagctcgta catgaacacg tagcgcaggt tgagcttgcg 61680 ccgcgagacc gggatgccga tgtgccgaca caggtacgcg aactcgaggt acttcttcga 61740 gaagcggatg cggtccaggt tcttggagac gtactgcagc atgttgcgca tgttgaaggg 61800 gatctcgcgc acggcgggct ccgcggcgtc gtcgaaggcg gtgcgcagat cgctggtgcg 61860 ctgtacgacc acggcttcgc cggtggcgtc gtcgtgcacc agcacgttaa cgcgccgctg 61920 ccggatgacc atgtcgaagg tgttgaagaa catctcgtac atgctgtgcc gagtgtcgtc 61980 cgcgatgcgc tcgcccaccg agaggctcgc ggtggcgtcg tcacgcacct gcttctcgaa 62040 cttgtacccg atgtaggaga atatcgagat cagcgtggcg tcgtcggcgt cggggttctg 62100 ctccatggtc gcgaagagca ggcggatgtc gtcctccgtg atcgcgtcca cgttgtacag 62160 gttgaccacg aagatggact tgttctcggc gatgaagtcc gtgtaggact tggtggccgt 62220 gttcgggtcg cgcatgtacg cgcggatctt cggcacgatg ctcgcgagga tggactccct 62280 ggaatccatt taaggacggc aagggcgcgc gagaccgtct caaaactgaa atcgtataaa 62340 ctcttaaaaa atcggtattg aaagtacgca ccaccaaata aagcgtcgag gtcgggcatg 62400 tcttcgtggc gactcaaaat gagcaagtgt tcaggttcca gcagcgtcca gactctcgag 62460 gatctgcgta atcgtcttcg ctccgaggcc ttgggcaacg attgccaaga gccccgcgac 62520 gacctcttcc ccagcggcga ggaggtgtctg gacatcgacg ggccctgccc ttgcgatgag 62580 gcggagcagg agatcgacca ggagcagttg cccgtgcccg aaaccgtgcc cgaaccgccg 62640 gccaagactc ctaagcgccg accagtgaag aaggataagg cagataaggc agataaggac 62700 aagtcgacca gaggcgcaaa gaaaccgtgc ccttcggacg acaaggatga cgagctcaag 62760 agcaacgacg tcgacaacaa cgaagagtcc ggcgacacag acggcggcgc gagcgcccga 62820 agccccagcg acatcgacaa cgtggacgaa atggacgact ccgacctcat ggtggcgttc 62880 tccaccatcc tcgcagactt caaggacctt acccaacgag tgaaagctct ttcgtccgtg 62940 ctcacggacg tgcaggcggc cggcatacgc aggagcttct cgacgctcgg caaggctctg 63000 acggaggcgg cccacatcgc caacaccgga tctaagccag tcactgcgcc tcgcaagaag 63060 aaggccgccg cctgcaagaa gtaggcgcac taaatagcga ggctcggtat gcgggcgctg 63120 cacctgtcag acggcaaact tttttttgac aaggagctga cgcagccggt ccccgacgac 63180 aaccccgcgt acgctgtcct tgcgaagatc cggatcccac cgcacctctc ggatgtggtc 63240 gtgtacgagc aggacctcga gtctgcgcag cagggcctca tcttcgtcgg gcgcgacgcc 63300 aagggccgaa agcagtactt ctacgggcgc ggacacgtgg agcggcgcac ggccgtccgc 63360 aacgccgtgt tcgtgcgcgt gcaccgcgtc atgaacaaga taaacgcctt catcgacgac 63420 cacctcgcct ccggcagcga ggccgaggcg cagatggccg ccttcctgct catggagacg 63480 agcttcttca tccgcgtcgg caagacgcgc tacgagcgcg agagcggcac cgtgggcatg 63540 ctcacgctgc gcaacaagca cctcgccgag gccgagggcg gtgaggagat ccgcgtcgcc 63600 ttcgtgggca aggaccgagt cgcgcacgag tttgccgtgc gcgaggggca gcggctcttc 63660 gcggcgctgc gtcggctctg ggacccgggc gcgcccgaca ggctgctgtt cgaccggctg 63720 agcgagcgcc gcgtgtacac cttcatgcga cgcttcggca tccgcgtcaa ggacctgcgc 63780 acctacggcg tgaactacac cttcctgtac aacttctggt ccaacgtgcg ctcgctggag 63840 ccgcgtccct ccgtgaagtc gctcatctgc acctccgtgc ggcagaccgc cgagacggtg 63900 gggcacacgc cctcgatctc gcgcagcgcc tacatggcca ccgcggtgct cgagctcgtc 63960 agggacggcg cgttcctgga cagagtcgcc gccaccgaca cgctcgacga cttcgtggac 64020 atcgtcgtgg actatgtaaa taactctgag caggtaaatg gatgaggcgc tgcgcgtggc 64080 ggcgcgcgtc gtggacgggc tccggccgct ggacgtggcc gtgtgtctcg cgcagctgcg 64140 cggagccgcg cccgagcgcc gcttcccggc gctcgacgag tgctccggcg aggccttcct 64200 ggactttgag ttcgccggcg gggacgtggc gtcgcggtac ctctccgcgc acacgcgcga 64260 gctccgtgcg gcggagcggc gcgagcacat ggccgcgatc gcgcgctgcg tcaccgaggc 64320 cgacctggcg ctcgcagacc gcccccgggg caaggcgcgc gcggcgctgc gcgtgtgccg 64380 caaccgcgag aaagtcgcgc gcttggcgag gctgctgcgc gacgccgaga gcagcggcgc 64440 ggacttcgcc ttcatacgcg cggccgtggc gtagcaaaac gtaaaaacaa cacattccct 64500 aaatcgccat ggacgcgcca agtctcgact gcatgctcgc cgcactcgcg gcgaaggcgg 64560 cctcggtgga ccgaggcgct cccgaggacg aggtgcacca cgaagtggag ctcgtgctcg 64620 tggacccgcc gctgtccacc ctggccgcca cgctgcgcct ggcctcggag acggagtcct 64680 tcatcctctt cacggtgacc gcgctcgcca aggaggaggg caagctgcgc gcgcgcgtgc 64740 ccatgtcgcg cgtcgtcggc ctggacgtga agaacgtgca gctggtcaac gccatcgaca 64800 gcatcgtctg ggagcgcaag gcgctcgtgg aggagaccgc gctgcaggaa ggctgtctgc 64860 tgcgccactc caccgagcgg cggcacctct tcgtggacta caagaagtac ctctcggcca 64920 tccgcgtgga gctggtaaac cgcgtgcgcg tgcgctccaa agaagtcgtc gcggacttca 64980 agttcaagta ctttctgggg tccggcgcgc aggccaagag ctcgctgctg cacgcactca 65040 accaccccaa ggtgcggccc tcgcccacgc tggagttcga ggtcgtcccc gcgggcgagg 65100 ccgtggacga ggccgccgtg ctcgcggagc tgcgcgccgt ggcgaaggcg ctcttcatgg 65160 cgcccaccga cgccgtcttc ctggcgccgc cggccgagat gccggtgcgc acgctcatgc 65220 tgcagaagca ggagatcccc gcgctagacc tcgacggcct tttcgcggtc tccaagacgg 65280 acggcgtctc cgcgagcgtg tgcgtggacg aggacggcgt cttctgcgcg ttctcgcacc 65340 tcgcgtacac catccggtac ccgctcgcgc gcgaagtgca gggccggtac cggctctggt 65400 gcgaggccgt gcggcccgtg ggcgagcgcg tgtggtccat gttcgtgctg gtcgtggagg 65460 agcctgcggg cgatgaccgc gtcgcggccg tggccggcgc cgtggaggcg ctgcgcggcg 65520 tgtgtgcacg cgtcgagttc aaacctaagc gcgtggacgg gcccttctcg gcgacctccg 65580 agctggtgga gcacatcaag agcgcgctgc agacggagcc agagggcgtg gtgctcttct 65640 acgcgcgcgg agagaagtcc aagcgcgacc tcaaggtcaa gcgcgacaac acggtggacc 65700 agaccacgaa cgtgatgttc cggtacatgt ccagcgagcc catcgtcttc ggcgagggct 65760 ccaccttcct ggagttcaag cggtacagca acgaccgcgg gttccccaag gagtacggcg 65820 cggggcgcat cttcctgcgc gaggacgtgg tctaccacaa caacatctac tgcatcgagt 65880 tcacgaagac gcacctggag gtgggcctcc gcagcgtggt cgtgcccgtg aagttcatcg 65940 gcgagttctc gcaggagggg tacctgctgc ggccgcgcct ggccaaaacg gagtgctact 66000 tccgcaaccc ctcattctac gggaaccagc actcggtggt gctcgagcac actcgcgacc 66060 agctgctctc ggtgggggac gtgttcgacg agagccgcat ggccgccgtc gggcagacgc 66120 tggccaacga cgccttccgc ctgaacccgg acacgcccta cttcaccaac cgacgcacgc 66180 gcgggccgct gggcgtgctc tccaactacg tgaagacgct catgatatcg ctgtactgct 66240 cgaagacctt cctgaacaac gccgagcgac gcaaggtgct ggccgtggac ttcggcaacg 66300 gcgcggacct ggagaagtac ttcttcggcg agatcgcgtc catggtggcc acggacccgg 66360 acgcgcgcgc gatcgagcgc gccatggagc gctacaaccg cctcaacgcg gggctgaagt 66420 cgcgctacta caagtttaac tacatccagg agaccatccg atccgagacc tacgtggaga 66480 gcatccgcca ggtcatgtac ttcgggcgct tcaacatcgt ggactggcag atggccatcc 66540 actactcctt ccacccgcgg cacttcgcca cggtgatgcg caacctgcgc gagctcaccg 66600 cgcccggctg caaggtgctc atcaccacca tggacgggga cttcctgtcg acgctctccg 66660 agaagaccag cttcgtgatc aaccgcaacc tgcaggagag cgaaaacttc atgtcgatcg 66720 agcgcgtggc cgatgaccag gtcatggtct acgcgccctc gaccatggcg cagcccatga 66780 cggagtacat cgtgcgccgc gcggacatcg tcaagctctt cgcggacaac ggcttcgacc 66840 tcgtggacca cgcgaacttc gagaccgtga tccggcgcag ccgccgcttc gtcgagggcg 66900 tctcgcggct ggagacgcgg ccctccacca agaacttctt cgagctcaac cgcaacgcgc 66960 tcacggagat ggacagcacc gacgtggccg cgctgctaaa gatctacgtg ctgtacgtct 67020 tcagcaagcg gtaggcagaa ccagggcgtc gattccgcgc ccgcgccggc gcggaaggcg 67080 ttgaacagct ccgccagcca ggctgcggtc tcgcgcgcgt cgatcgggcc gccgtcgtcc 67140 ggcggcggct cgcgcgccgc gcgcaacacc agcgtctccg cgggcggcag aggctccaga 67200 gcctcgaaga ccgcgcggct cgggaacagc gcgcgcatca tgcgcgcgcg gtggccgaac 67260 accgccttga ccgcgcgcag tgccgagcgg ttgtccagcc gcagcgctcg gtcaaaacga 67320 tgcacgcgcg cgggcgcgcc gcggtggtcg cgctccacga gcacgtgccg ccacgccagc 67380 gccgcgccga cgcggtccag gctgggcgcg agcgccacca ggcttttcag cgcatgtaaa 67440 tctccgcgca tggccgacgg ctccatttac tactgcggag gaacgcacgt ggtcgcggcc 67500 gcgccgggcg ccgcgcttgt ggtgctggac gcgcccggtg cggcggcggc ggccgcgccc 67560 gcggggcagc gcgtcttctt cgccgagtac ggcctcgaga agcgggccgg cggcccgatc 67620 acggcgcggc tgcgccgctc cgggttccgc ggcgccgcga acgcctgggc ctccgtggcg 67680 gacttcgagg ccggcggccg tccctccgcg tggacgctgc gcgcggagga ggcttcgcgc 67740 gtgccgctgc cgacggacgc ggcgctggtc ctggcctggg gcgcgcgcga ggagccgctg 67800 cgggcgtgcg tgctggcgcg cgcggcagac gcggaggcgc cggtgggcgc cgcgctcaaa 67860 gaagccgcct tcgacgcgcg ggcgccggcg gccgcgctgt tcgcggcgct gggcgcgccc 67920 gcgctcgcgc ccccgctgcg ggcgcggcta gtggcgccgc cgggcgcgcc gccgcggacg 67980 cggctctgcg agaacccggc catgctgcgc gcgttcgcgg tgggctggtt cggcgcgcag 68040 ctgggcgagg cctccgaaaa tgaaaaggta tttgccgcct ttgataaggc gaggtcgtgt 68100 ttggacgacc gctgatggcg acgcccgcga acgcgcccgc gctgctcgtc gcggcgctgc 68160 gacaccgccc gtaccgcgtg gagtaccacc cggactggga gccggtcatc gagacgctgg 68220 tggacgagta cgacgcggtc gcgccctggc tgctgcgcga cgcgacgagc cccgagcccg 68280 agcgcttctt cgcgcagctg gcgaagccgc tggcggacaa gcgagtgtgc gtgtgcggca 68340 tcgacccgta cccgcgcggc ggcaccggcg tgcccttcca gtccccggac ttcagcaaga 68400 agaccatccg cgcgatcgcg agctcggtcg cgcgcacgac cggcacgcag ggctacgcga 68460 actacgacct ggacgcggtt ccgggcgtgc tgccctggaa ctactacctc tcctgccgcg 68520 agggcgagac caagagccac gcgatgtact gggagcgcat ctcgcggctg ctgctgcagc 68580 acgtggccaa gcacgtgagc gtgctctact gcatggggcg cacggacttc cagaacgtgc 68640 gcgcgcgcct ggacgtgccg gtgacgctgg tggtgggctt ccaccccgcg gcgcgcgacg 68700 ggcagttcgc gcgcgagcgg gccttcgagg tcatcaacgc cttattggag ctcaacggga 68760 agtctcaagt ggactgggcg cgaggatttt ctttttatag tgaaaattaa tccgtggtcc 68820 taaatggcgg cgcccatatg cgataactct cacgtgttcc tcctcaagcg cctgggcgtg 68880 ccgtcttcct gccggcgctc ggaggacccg cgcttcgtgg agatcctgac tcccttcgag 68940 ctctcaaact acatcgagcg gcacccggga tgctgcctct tcgagacgct gcgcgacgag 69000 gaggactgct ccgtcgtgcg cgtcttcgcg gacgtggaca tggacagcgt gctcgaggag 69060 gaggacttcg tcgcggcgct ggaggacctc atcgtggagc tcgcggcctt cttcgaccgc 69120 ttcgcgagcg gctcctgcgg caccgtgccc ggcgaggtca agcgcgccat gctcgcgaac 69180 ttctcggtca cgcgatccac ggccgagcac aagaccagct tccacctgat cttcacggag 69240 acgtacacca cgctggacac gctggtggcg gcgaagcgcc cgctgctgga cctggtgccgg 69300 cgctcggaca acgtgctgct gcgcgcgctg gacacggccg tgtaccgccg cggcgcgacg 69360 ctgcgcgtgg tgggcacgcg caagacgccg gagtcgagcg cggtccaccg catgcagtcg 69420 cccgacgacg acatcaagga ctacctgttc acgttcgtgg agctctcgga cgcgagcgtg 69480 tacttcgagc tcgcggagcg cgagcagcac acgctgagca ccgtctgctg ggagacctcc 69540 tacatcccct tcggcgacgc gatgcggcgc gtgtgccagg cggtggtcaa cgacatcgtg 69600 aacctccgcg acatcaccga ggacaacttc ctcgacacgc cgctggtcat cgactacgcg 69660 acgcgctgcg cgctgtgcaa gaagcccaag cacaagcacg cgcaccacat caccatgggc 69720 aacggctgcc tgcgcctggt caagggcggg aacgcgcaca gctgcaaggt caagatcatc 69780 cagctcgagg gcaaccggct cttcacggcc gcgcagatca tcatcgcgtc cgaggtcgtg 69840 aagctcaccg agcgcaacga ctacatcgtg tggctgaaca actcctggcg cttcagcgcg 69900 gaggagtcgc tcatcaccaa gctcatcctg gacgtgcggc actcgctgcc cgcggactac 69960 gccaacgaca tgctgtgtcc gcgcaagcgc aaggtcgtgg agaccaacat ccgcgacatg 70020 ctcgtggaca tctccgagac ggacacgcag tacgacaagc tgcccttcac gaacggcgtg 70080 ctggacctgg ccacgggcga gttcctcacc ggcgaccgcg cgaaggcctg cgtgtgcacg 70140 gtctccaccg ggtacgcctt ctcgcgcgag gagttcgcgg ccgcggcgga ctcggaggcc 70200 atgcgccggc tggtcggcgt catcgacgac atccagccgg acacgcccga gaacgccgat 70260 aaccgcgcgc tgtacgagcg cgccatgtcc agcgcgctct gcggcgccac gaagacggtc 70320 atcgtcttct tctacggcga caccatgacc ggcaagtcca cgagcaagcg tctgctcatg 70380 tccgcgctcg gcggactctt catcgagacc gggcagaccg tgctcacgga cgtgctcgac 70440 aagggcccga accccttcgt ggccaacatg cacctgcggc gcgcggtctt ctgcagcgag 70500 ctcccggact tcgcctgcaa caacgcgcgc aagctgcgct ccgacaactt caagaagctg 70560 accgagccct gcatcgtggg ccggccctgc ttctccaaca agatccacaa ccgcaaccac 70620 gccaccttca tcatcgacac caactaccgc ccggtcttcg accgcgtgga caacgcgctc 70680 atgcgccgcg tggcgctggt gcgcttccgc acgcacttct cctcgtcggc cactcgcgcg 70740 gccgccgcgc acaacgtcga gtacagcgcg gtcaaggaga tggacgagag cctggacacc 70800 aagatccagc gcaactactt ccgctacgcc ttcctgcgcc tgctcgtgca gtggttcggc 70860 aagtaccacg tcccgcaggt ctcgctggcg cccacgcccg acgcggtccc cgacttcgcc 70920 ttccaccgcc gcgtggccga gctggtggtg gccagcaacg acgcgcaccg ccgcgcgatg 70980 gagtcgctgt ccaagctggg gtacgtgctc gtgggcggca acgtggccat gcccgcggac 71040 gccttccggc agcggctggc cgcgcacttc aacgcgcgcg tgcacggcgg cgacatagac 71100 gccttcatgt tcaagcacaa gaaggtcgtc aacgtaacgg aggagtacgt ggagtacgta 71160 ttcatcgaag atgtcgagaa taaatagacg ggtatgaact cggacgtgat aaagctgttc 71220 gtcgggcacg acgagtccgt gcccggcatc ctgccgcacc agctcgcgac cgtggacttc 71280 ctgatacgcc gcgttctaga cgacaacgtc agcgtgcttc tcttccacat catgggctct 71340 gggaagaccg tcatcgcgct gctgttcgcg atggtggcct cgcgcaccaa gaaggtgtac 71400 atcctggtgc ccaacgtgaa cgtcatgaac atattcaact acagcatggt catggtcgct 71460 aacctgttca acgcgccctt cgtggccgag aacatattcg tgtactcgac gactagtttt 71520 tattcgctaa actgcaacga cggcgtcata aactacaacg gcctcggcaa gtacgagaac 71580 tcggtcttcg tggtcgacga ggcgcacaac atcttcggga acaacaccgg cgagctcatg 71640 atggtgatca agaacaagac gcgcgtgccc ttcctgctgc tctcggcctc gccgatcacg 71700 aacacgccgc tcacgctcag cagcatcatc agcctcatgt ccgagaagga cgtggacgtc 71760 ggcgacatcg tggtgcaggg caagaaggtg ttccagatcc tgctgaacga gcacggcgtg 71820 cgcgtgatcc gcgaggtgct caaggggcgc atctcctact acgagatgcc ggacacggac 71880 atgcccgagg tgctctacca cgggcgccgc ttcctggaca cgcgcgtggt ctactgccgc 71940 atgtcgcgcc ggcaggagga cgactacctc accgtgcgcc ggctctgcaa caacgagatg 72000 ttcgagaaga acatgaacaa cgtgtccatg gcggtgctgg gcccgctgaa cctggtgaac 72060 aacctggacg tgctcttcca ggcgcaggac aaggacctgt acccgaacct gcgcatcagc 72120 aacggcgtgc tctacgggaa cgagctcacc aagctggaca tcagctgcaa gttcaagttc 72180 ttcatctcga aggtgggcgc catgcgcggg aagcacttca tctacttctc caactcgacc 72240 tacggcagcc tggtcatccg caacgtgatg ctcagcaacg ggtactcgga gttcggcggc 72300 tcgcagagca acaatccgca caccacgccc gacgggcgcg ccaagacctt cgcgatcgtg 72360 accagcaaga tgaaggcctc gctggaggag ctgctcgagg tgtacaactc cgcggagaac 72420 aacgacggtg gcaagctcat gttcctcttc tcctcgaaca tcatgtccga gtcctacacg 72480 ctcaaggagg tgcggcacat ctggttcatg accatccccg acaccttctc gcagttcaac 72540 cagatcctgg gccgcgccgt gcgcaagttc tcctacgcgg acgtggccgc gcccgtgaac 72600 gtgtacctca tggcggcggt gtactcggac ttcgacgagg acatcgtctc gctggaggac 72660 tacagcgtgg aggacctcaa cgcgctgccc ttcgacgtga agaagctctt ctacctcaag 72720 ttcaaggcca aggaaaccaa ccgcgtgtac gccatcctgc aggagctctc ggacgcgtac 72780 tccgcgcgcc cgcacccgca gctcgtggac gtggtgctgg gggagatcgt gcgccagttc 72840 ttcgcacggc actgccgcgt gcccgccgag gacgccgcgc tcgtggccgc cgtcgaggcc 72900 gttctcggca cgcgcgaggc agcggccgag tacatccgcg cgatagtgga cggacacttc 72960 ttcgtgacca acaagacctt cgggaagtgc ctgctcttcc ggcacgagcg cgacatcgtg 73020 accgtgccct tcgagctcga gcacgacccc ttcgcgtggg cgatcaactt ccgcaaggag 73080 gtcagtgtgg tgaatatata acggcaaaca taaatagaaa gactgtcctt ttgcgcgatg 73140 tcgaccttcc ggcagacggt gtacctggcg gtgacgctgc agccgcacga gctcacgctc 73200 gacttccgcg gcaacgtcgc ggaggcggtc atgcgcgagt acctctacaa ggagaagggc 73260 gggctcatgg ccaccgacat cgaggtctgc ctcggaaacg agatgccgct ggggcgcatc 73320 gtgaacaacg cggttgtggt ctcggtgccc tgcaacgtga ccttcaagta ctaccgcgtc 73380 ggcgacaccg tgagcggcac gctcaacgtc gaggacgaga ccaacgtctt cgtggactgc 73440 ggagacctca tctgccagct cggcaagagc tcgggcggcg tgaccttcaa cgagtccaag 73500 tactgcctcg tgcgcaacgg agtcgtctac gagcacggca gccgggtctc ggctgtgctg 73560 cgcgaggcgc gctccggacg cgagtccgcg ttcgtgttct ccgcagtgct gctggacggc 73620 gtccccgccg aggagaagga cgagaagaag gacgagggcg agaaggccgc ggaggaggag 73680 acgcccgcga gccccgccgc caaaaactag cattattggg ccgcgcgaac cttcgataaa 73740 tgcgcacgta cacgtcgctg ctctcgaagc tgctcaagag caaccggcgg ctcgggagca 73800 cgcgcgtctt ccgcgacccg ctgcagcaca tcagcgcgac cgcctttgtg caccggcgca 73860 tcgaccggca ccggcgcgtc tccatctgcg ccgtgctcac caccaccgac gggctcgtgg 73920 tcgcgtgccg gcgccggtac tcctttttgt cctccgagct cgcggagacg cgctcgcccg 73980 cgcggcgcgt gctgctcgca accaagcacg cggacgctct cgcgcgcctc ggcgccgcgc 74040 gcccgcgcga cgacgtcatg tttccgggcg gcgccccgct gtccggggag tcgccgctgg 74100 cgtgcgtgct gcgcgaggtc gaggaggaga ccgggctgcg cggcgaccag gtcagcgtgg 74160 acgagcggct gttcgtgcac gccttcatcg acgacctggt ctcgggccgc gacttcgacg 74220 cgatcatctt cacgggcgca gtcgcgcttt cgagcgcgga ggtggcgaag cagttccggc 74280 ccaacgacga ggtcaagggg ctggtcttcc tgcaccccga ggacgcggag ggcgtgggcg 74340 tgatggcgcg gctggcggcg ttcgcgcgct gcgcggcgcg cctgcgctgc tggggcgcgg 74400 ccgtcacgcg atagaggcgg ggtccaccac gtacacgagg cgcccgccgc tcacgcgcac 74460 ggtgggcggg tcgcccagcg cggtcaggaa gttcccgtcg tcgtcgaaga ggcgcccgcc 74520 gcgctcgagg aagcccttgc gcaccgtgac cagcgccgtg gaggtggagt accacacgct 74580 ctgcccgtcc gcgagccgcg ccgcgcgcgc gggcccgcgc gcgtccgccg ggcgcgccac 74640 cagcgcggac cagccggagt cgtcctccag cggcgcgaag tccgtgaagg cctcgcgcac 74700 ccactccagc gagcagcgct tgagcacgcg gaagagctgc gtgaactgcc gggacttgtc 74760 gcggatgagg gccagcaggt cctcgtccac ggtggcggcg ccggagtcct ggcgcgcgac 74820 cacgaagtgc acgttcacgt agcggcggtc gggcggcgtc atctcgtggc tgttcaggcg 74880 caccgcgcgg cccacgatct ggcgcagcga ggcctcgttc caggtcatgt ccaggatgaa 74940 gatgtcgttg atggagagga agctgaggcc ctcggagccg ctcagcgaga acacacagac 75000 cttgatcttc tcgccgtcgg tgttgtcgca ggcgttgaag gcgtccacga gcttggcgcg 75060 cgtgtcgcgc gtgcgcgagg agaactccac gctggagacg ccgaaggcgc ggaagtagag 75120 cagcagcatc tcgatgccgg tcacgttgac gaagggctcg aagaccagac acttgcccgg 75180 cgaggccagg atgcgcaggc agacctcggt gtacttgcag ctgcgctcgc gcagctccgc 75240 gagcagcgag acgtccgcgg aggtcatgcg gtcgccgctg acgggcgcgc cgctgcggaa 75300 gagccgcatg gccgcctccg agaagacgcg gtccttgacg gcgcgcgcga agtccaggaa 75360 gagcgcggcc acggcctcgt cgtactcctg cttggagagc acggacttgt cgggcgcgtc 75420 ctcgaaggcg aaggtggccg cgatgcgccg gtacacgcgg aagaccgcgg cgccggactt 75480 gcgctccatg gcggccgcgc ggcggtaggc ctcggtctgc ttcgcggtca tgtccacgta 75540 catcatgcgc acgcgcttgc gcgcgaaggc ggcggagccg tcgacgtcgt cgaagatgga 75600 ggcctcgttg gtgactaagt acgagcacag gccgccgagc ttgtccacga ggtcctcggg 75660 gttcgcgagc gcgccgccgt tgaagagcgg cgtctgcccg accacgccgg ggcgcagcag 75720 gttcacggcc atggagaact ccttgacgct gttcaccacc ggcgtggccg tgaggcagag 75780 cagcttcccg cggcccatgg ggatgttctt cgcgaggtag ttgtacaccg tgcgcgcggg 75840 ccgctggcgc ccgtcctcct tggtcagcga catcgagatg aagttgtgga actcgtcgat 75900 gaccacgcag acgcggctgc tcgacgaggc ggtcttcatc agcgtgaaga agcggtggtg 75960 gaagcgcggg tcgtcgtagt tgatgaaggt gcacccgggc acggcctcgg gcgcgaagcg 76020 catcatcgtc gaggtccagg gctgctccac gagcgccttc ttcacgagca cgaccaccgt 76080 ccagtccgtg aagacgtcgc gcaggtgctt gagcacgtac accgcggtca cggtcttgcc 76140 cacgcccgtc tcgtggaaga gcagcagcga gtgcatgctg tccaggccca ggaacacgcg 76200 cgccacgaag agctggtagt ccttgaggcg cacggactcc tccacgccct gcatctcgga 76260 gggcatgtgc gcggtgcgcc gcagcgcgta gtcgatgtag gccgcgtgcg cgctggtcat 76320 ggcgacggtc ggcgctcctt ttacggggtc tgtcgtctat ctattgtcgg cgcgggtctg 76380 atttaggggc agtagttaca aaaacgtttc cgctgctcgg cgcggcgttt ggaggagcgg 76440 ttgcggccgc ggcggcgcag gcgcgcgcgg cgcgtcttcg tggtgcggtg gccgaaccag 76500 cgccggtgca tgaccgggtg cgagaccgcg gccgcgcgat ccgcgctcat gcaggttgcg 76560 taggtgcggc acatgctgcg cagcacgcgc cgcgtgcgcc gctccacggc gtcgagccgc 76620 ctcgcgacga tgggaaagag ccggcgccag ccgcgcacgg cgaagagcgg gcgctcgcag 76680 accgggcgcg cgagcgcgtg gtaggcgccc agcagccgcg ggtccagcga gcgcacgtag 76740 gtctccacga agccgttgcc gaagacgatg gcctgtgcgc atagcgggtt cgtcatctcc 76800 ctcttggagg cgatggcgtc gcccacgaag gcgcgcacgc cgcagtgccg cagcaccagg 76860 cgccgccgcg ggaagtgcag gtgcgggccg agcgccgcgc gggcggcggg gatgtgcagc 76920 cgcggagaaa aacgcgcgcg tccctccatg gcatctaagc gctccgtctg ttttcagtta 76980 tatcgccgcg ggcggctact gcagcagcag cttgagcttg cgctggctct cgttctcgat 77040 gctcttggac tcggaggtca tgctctcgta gagcagcgag tgcgtgacgt agagcgcctc 77100 gtacacgcgg ctggcgaagg ccacgaagcg gtccacgaac tcgctctcta cggggtcctt 77160 gagcacgcgg aagggcacgg ccagcgcgtc gcgccaggcg gcggccttgg tgcgctcgcg 77220 cacgtgcgtc acgaaggcgg cgatggccgc gcgccgcggc tcgctggcga ccatgacggc 77280 gctgtccttg agccagctgt cgctcacgca cttgaagagg cgcacggtgc cgaagaggct 77340 gcagtacacg cgcagcgcgt gcaccacgtc ggtgccgaag agcgtgggca gcttgagcac 77400 cacgaagcgc tcctgcgtga tctcgagcag cgggcgcatc accgcgaagg tgatcgcgtg 77460 gtagtcagcc acgtagaggt tgttctcggt gaggtggttg ttggagcgga tggcgccgcg 77520 ctccttgcgg tagagccggt tgcgcgcgct gaggtcgagc acgaccgcgt cggccctgcc 77580 gcgcgctctg gagcgcacgc tggtgatgcc gtgcgcctcg agcaccttct cgacgtcgcg 77640 ctcgtcgatc atgaggtcgt gcgtgtacag actcagcatc tccgtgggca tgcggttgat 77700 gtcgttcacg cgcgagcact gcaggaagta gttggtcccg taggccaggc tgggcaggtg 77760 cccgacgccg agctgcaggt ccagcgcggg cgtcgagtcg aaggtgggca gcgtcacgct 77820 gagcccctcg cggatgctgc ggcgcacggc ctccaccgcg tccatggccg atttatgga 77880 cgcacagtct gttttcattt cgcggctact gcgcagtcac cttctcggcc acgatccccg 77940 cgtcgtagct gagccggtac acctcgttgc acaccacgac catctgccgc ggcacgtaca 78000 tgagcgggtt gtgcgcctcc atgtgcgcgg tggtcacgcg caccgccagc ttgtccttgc 78060 ccctggagac gttggagttc agcgcggtgg gcgagaagaa ggtgctgggc gtaaagttga 78120 actgcagcgt gcgcacgccg ggcgtcttgc cgaggatctc gccgaagacg cgcgagactg 78180 cgctgttctc cgagtacagc acctcgttgc cgaagcgcac gtccatgcgc gcgatgacgt 78240 cgatcttgtt cttgaagtcc acgcccttga ggaagggggtc ggccacgaag aggtccttgg 78300 cgcgcgcctc cggcgagcgg ttgtcgccgt tgtacacgtt gcgctggcag gtccacacgc 78360 ccacgggcac ggaggcgtcg ccgatgttca cggagtggat ggcggtcgtg aagcggatgc 78420 gggaggtcgc gcggctgtag gcccccgtga tggcggagaa cttcttggac atgttgtaca 78480 cgacggagtt cttcctggtg gcgaacacta ggatgttcgt gtgcaggaac acgcgcatgc 78540 ccacgggcac gtcgtcgatg cgcacgaaga cgtcggtgtc ctggatggac acgacgcccg 78600 acgggggcac ctcgactatc tccgcggtct cggggaagcc ctcggggtag cagttcgaga 78660 cgatcaccat gtcctccagc aggcgctcca cgaaggccat cacgaagtcg ccctcggact 78720 gctggaagcc ggggtacgat atgaagcggt tgttggcgtc gctgagcacg ggcttcatgt 78780 acacggacag ggaggtgcac gcgtgcacgt ccgtgatcac cgcggtggtg tggttgatct 78840 gctccacgcg ccgccgcggc atctcgatga aggccgggcg cgggcacagg ttcttgacca 78900 tgtagccgat gaagctcagc tccatggagt aggggaactc cttggcgagc ttggcggcgt 78960 cgaaggtctc gtcgtagacc atgacgcagg cgacggggtt cagcgtgacc gtgaccgtga 79020 ccttgctgtc gctgagcttg agcgtgctga aggtcttgtc cgcgtcaaag ggcgtcttga 79080 tgtaggcgtg cacgcaggcg gcctccttga tgacgtcgtt gggcgagctc ccggtggaga 79140 ggtcgttgag ctcgcgcgag aagcccgaga gctccatcac gcgctcgttg tccaggcagg 79200 agtcgaacag ctcctcgccg gaggtctccc agatggtgtc cgcggcggag ttcacggcca 79260 cgtggcggat gagcttgtac gcgatgtagg gcacgtagca catcttgccc acgcccttta 79320 tctcgggcag gtccacgctc agcacgaagt tgttcatggc cgagatgtac ttgtcgcgga 79380 tctcgaaggt cacggtgacc gcgtcgctgg tggtgtccac cacgccctgc gtggtgatgt 79440 actgcggcat gtacaccgtg ggcgcgcggt ggtccgtggc gaacacgctg gcgcgccgca 79500 cggcgtcgtc gccgcccacc aggctcacca cggagttat catttatcc ctgggaaaac 79560 cagttaaata aggctcttca gagccatgcg caccgtccgg ccgtcgggct ccaggtagca 79620 gcgcccgtag acgccctccg tggcgcgcgt ctcgttgatg agcgcgcgca cgcggtcggg 79680 gtccgcgtac atctccagcg gcagcagctc gatcttgggc tcctcgcgca gcgcgacgag 79740 gtgccggatg gagcccgcga aggagtcgcg gcacaaccgc gagcagaact cgcccacggc 79800 gccgccgtcg agcgtctcca cggccagcgc ggccgtgccc acgcgctgac ggcagaacca 79860 gcacgtgccg tccgcggcgc gcagcgccag ccgctccgcg gacaccgtgt tgaagtactt 79920 cggcagcacg tactcgatgc ggcacgccgc cggcggcgcg caggccgacg cccgcggcgc 79980 ggatatgtcc acccgcgaga gcgcgatgcg cttcatgggc ggcggtggct gctatttatg 80040 tcgcccgcgg cttttcaaag gtcgagcgag cacgccgcga agcgcgcggg cgagaacacg 80100 tactcgtggc cgaactccgg gatctgcgcg gcgcgcttgc gcgcgcgcat gtgcgcgagg 80160 aagttctccc aggtgagctg gttgctgttg ttcttcgcgt agttcttcac ggtctgcgga 80220 cgcaggttgc gcgtcacgcc cgtgacctcg aagatcttgt ccaggaagaa ggagtagttg 80280 atggttttgg tgggcgtgat ctcctggcag aagaagacca gctgcttgaa tatctcgatg 80340 acctcgttga tcttctcggt gctgaggtcc agcttctcgt ttttgacctg gttgatgatc 80400 tcgaagacca gcttgtagtc cttcttgttg atcatttcgc tgtccttgag gaagctggag 80460 acgtagttgg cgtccacgtc ctcgggccgg atctggtgcc ggtccatcat cgcgcgcagg 80520 tcgcggatga cctcctccga gcactgcttg gagagcagcc gccggagcac gttccgcagg 80580 tggatgagct tgttcgacac gtggaagttg gacctcttct gcacgcggat gcccatggga 80640 aacacggtct cgcagaacag gcagaactcg tagtccgcgt cggacacgag cccgttgcgg 80700 cggcagccgc cgcacatgcg caggttcatg cttgctccag ccccagcacg cgcaggatct 80760 cgcggtccag cactttagtg tccagcgtgc gggttctaca gaactggagg aagcccgcga 80820 gcgcgcgcgc gcgccctggc tgcgagagca gcagcatgcg cgcgttctcg gggtcctcgt 80880 tgatgacgcg cgtgaggttc agcgagcacc gcgtgcagcg ccgcggcggg tcgagctcga 80940 ccgagtacgc cgcgaaccag acgttgtcgc ccatgtatta tttattaaca cagaacgtcg 81000 cacatgttgc gcgaggacat gtacgggtcg tactcctgcc cgtagatgag gatggtgcag 81060 taccgcgaga tcatgagcat ggcctcctcc atggtgagca ggtcgtcctc gaacatggcc 81120 ttgtgctgca tgtgctggct ctgcttggcg gccatcgcgg ccgcgccgtc gccgcgcagc 81180 cactcgttca gacactggcc gtcgccgccg gcgccgctct cctgcgcgaa ggtgttgcgc 81240 atggcgcgca tgagcctggc ctccctggcc gagcggctga gcacggtcat ggggtcgtag 81300 agccaggggc ctgcgtccgt gaacaggatg gtgcagtacc cgttggcgaa ggcgtccgcg 81360 ccgctgcagt tgtcgatgcc gtcgccgacc ctgtagcaca ccgcggagac cagccggtac 81420 atgatgccgt tgagcatcat gtcctgcgac acctcgatgg gaatgtcgct gatcacgggc 81480 cgcatgttcg tgaagcagtc gcccgtgctg gccatgcccc cgcgccggtt caccaggaac 81540 accagcacgc cgttcgtgat cacgggcgcg cggtcgcgct cgtagaggta gccgctcgcc 81600 gcgcacacgg cggacgccac gtccgtgcgc gagaccgcgc ccatgttctg ggcgggcatg 81660 tacagcactc gcccggcctc cgcggtgcac gagaagggct gctccccgcc cacgtggatg 81720 ggcgccgtcg atgtcgtgat catcttgctg gagtccacca ccaggtaggg caccgtgtgc 81780 atggccatgt cgcccatgcc cccgatcccc gttccgaacg acggccgcga cacgctcacg 81840 agcgtcggct tgaacgagac tatggagaag atggagggcca agatctgctc ctcgtcggtc 81900 atgatggagg cgcacgaggg gtggatgatc ttcattaggg cgttgtcgat ggactcgtcg 81960 ctctcgcagt agaagacgcc catgcggagg ttcaggatgc accgccgcag gttggtgtgc 82020 agcaccgcgc gctggatctc catggacacg gagtcgccga cgccgggcat cacgatgggc 82080 gtttcctcgg tgagcttgtt caccagcagc tggtagttgt tgggtcgcac gcggctgttg 82140 tggtggagct gcgccaggag cgagaggctg tccccgttga cgaacgcgga ctcgatggcc 82200 ggcagcttta cgccgaacag cgccatggcg atggggtgca cgaagcccac ggagtcggac 82260 gacttgaacg agaagagcag gtcgcccgag gagctcatgt ctttgaagtg cacggactgg 82320 aactgcgtgg cggagagcaa gttctggtag ctggacatgc tctgcaggtc gtcgatctcc 82380 ttcatctgct tgtttacgcg ggtcgagttc ctcccgtaga tgatcaccag cgggtgcgtc 82440 tggctcacgg atagccccga gtccgtcatg gcggcgcgca cgctgttcag cagatcgaac 82500 agctccgacc ggtctctgtt ctggatcccg acctttgcca tcacagacat gagctcctgg 82560 atggtcatgt tcttgtggtc tcggcgcgtg gaccgcaggt agtcggcgat catctcgccc 82620 tccttacgga tcttcatctg ccagtcgtgc atggaggtca tgcggtccac aggcatgagc 82680 acgctgtcgg aggacgactg cgcggcgctg ccggactggc gcgagccagg gcgcgcggac 82740 gacgggcgcg cggagctgcc gcggctggag gaggacctgg acctccgcga ggatcttcgc 82800 tgcgaagagc tgcgcacggg ccgctgggcg cgcgccccgg cggaaaccat gtcctcgcgg 82860 tttatgctga ggagcgagct gcagaccgcg cacgacagcg actgctttgg aatgtggatg 82920 tggtcgcact ccagggacat gcccgcattg tcgtagcccg ggaccaagtc gaactttgca 82980 ttaaaaaaat ctgatgcgca cgcgggcgat tccatttata ccggaagttt ttatgaggtg 83040 ccggtattat ccacgcgatc tcgcagtgtg ctgggagact ctagcgtagc cacggacccc 83100 gtgagcagac gacgcaagtc gttgatggcc gactgcgtga cggacttcgc cgtctcgatg 83160 tcgcgcgtaa ggctgagcga ctcggcgttg aggtcgcgca cgctgtccgc gatgtcggcc 83220 agctcctttt tgatgaaatc cttatcatta tcggcgttga tgactttgtc cggcactcta 83280 gactctagaa ccggtgacgc ggcgggcgcc ttgatcgtcg ggcagctgga cgccgggtac 83340 tggggcggcg gcaatgattg ctgtaggaag atgggcttag cggcaggcgc cggttttgtc 83400 ggcaagggcg gcgccggcgg gcactgtcgt gtagacggcg ggcacgccgg cgcggggcac 83460 gccgccggtg gcggacatgt cggcgcagtt gcgggtggac acgcgggcgc gggcgccggc 83520 gcgggacacg tcgcggcagg agccgggcac gcgggagccg gagctggagc cgggcacggc 83580 gcggcaggag ccgggcacgt cgcggcaggc gcagggcacg cgggagccgg agccgggcac 83640 gccggcgcag gaggacatgc cggcgcagcg gcaggacaga ccaccgctgt cgcggagcac 83700 gcggcaaccg gcgtggagca cgcggcggggc attacgttca gaggcgtcga ctggaccttg 83760 gcaccgcggg gcagtagcga tggcgctagg ggcgactgtc cggtggttgg acgctgcatg 83820 caggcagtcg cagatttcag acgggactgg taatacctgc ccgcttcctt caccgtgtac 83880 ttgtcgacgg agtctacctc ctcatctgga ggacatggct gctccggtgc gggaacgact 83940 gtttgaggac acttggtgaa cagactggag ctggtctccg atagcaccag tttagacttg 84000 gccaagtcgg aggcaaacct tcttctgaga tccatttaag ccttcaaaat tgaacgtgta 84060 cgccgaccgc taaatggaag aatcggtggc cgtcgagtac gcggacgagg acgaagatga 84120 gattgaggag tacgaggagg aggacgatga cgaggaggaa gagtctgccg agggcgccgc 84180 cgcctcctcg gtcagcgacg tagcgctctc tgccgccgag aagctggtgg cctcggaggt 84240 cccggacgac gcggctgccg cggacaccaa cgtgcgtcaa cgcgtcaccg cgcgcgtgga 84300 ggagcttaag gcgcgctaca cacggcggat gagtctattt gagctcaccg gaattgtagc 84360 agagagtttc aatcttctgt gtcgcgggcg gctgccgctc gtggcggacg ccgcagaccc 84420 ggcgctcgac aacgagctaa aagtggtggt tcgggagctc gaggagggcg tctgccccat 84480 cgtcatcgag aaaaacggcg agttcctctc gccgggcgac ttcgaccccg agtgcctgcg 84540 ctaccacctg acgtacatga ccgacctctg gaagtcccag gggcgcatgt agccgcggct 84600 acgccgactc ggcggcctcc gcgatttttt cttttatcat gtccagcagc tcgcgcacca 84660 cgatggggcg gccgcagtac gtgatgccgt tttcggatat cacgctctgt gcgatgtcca 84720 ccagcgagcc ctcgcgctcc cagtactcgc gcgcgagcac ctccttgtac aacgcgcggt 84780 ggttggccac gtaccgcacc agcgtctgga tgttcttcac gcccacgctc ttgaggtcct 84840 gcggcgagaa cttctcgcgc agcgacacga agacgtcccg gacgagcttg ccgatctcca 84900 cgttggtctt gaactcgttg tacagcacca cgtagagctt gcacacgacc gtagcgaact 84960 tcgcgggctt gagatccttg ttctggaaga ccagcatgct gctcatcacc ttcttcatga 85020 aggccaggta cttcgcgcgg tcgccctcga cgctcacgct cccgacctcg aggtcggaca 85080 cgcagcggat tccgtgctcc gcgctctccg cggagacgcg cagcagctcc tggtactcct 85140 tgagcttctg cttgtccgtc atcagcgagt tgtcgaatac cgccaccagc ttgagcacgt 85200 agttctcgtc cgagaagacc ttgttcagac acttcaccag gaagctgtag tggctctgca 85260 ggatcttcat gaccgcgttg gcgccgctgg ctccgcggac gtgcgatatc atctccatga 85320 tcttcttaga gtcgtcgatg atctcctcgg tgtcgttgcg catgttgcgg tacattgcgt 85380 tcagcgagac cagcgtctgc gcggccagga gcacgtcgcg gaacacgcgc gcgaactcgc 85440 gcttctcctc cgcgtcggtg atgctgttgt acacggactt cgccaccgcg ttcgacttca 85500 ggaaccagaa ggagagcgcc tggtagttga agtgcttcat cagcgccagc acgtccgcct 85560 cgctcatttc cggcgcaatg gggcacaccg agctctcgag cacgggcacc atgctgacga 85620 gcgtgtccac gtccgtgtcg aagtccaggc agtccacgca gagcccggtg ccgcggctca 85680 ggtgatcgcg gctgatgtcg tagaagcgct cgtagcaggt gcggaggcgg tccatgtcgg 85740 ctgcgtttta gagagacaca cactcttgaa ttatggctgc gggtagaact cctgcagcag 85800 cgccggcgca cgcgcggagt ccggctccac tcccagcttc agcgcgcagt tcacggacca 85860 ggtcttcatg aagcggtcgg gcgcgtccgt gaccacgtgc cggaagagct tcgcgaagtg 85920 gcggctcacg gcgttgggca cggtcgcgtt gcgcacgaag gccgtgaagc gcgaggtcag 85980 cttcggcgcg aagcgcttgc cgtccacgaa gaagcccgag gtggtgagcg agagcccgtt 86040 ctcctcgcgc accacgcgtc gcgcggcctt gtgcggaaac atgctcgcga ggcgcccgct 86100 cgcgtcctgg tctaggtgga tggcgtccgt ggccgcgtcc ttgcggatgc gcaccacgtc 86160 gtgcacgatc tcctggatga ggatgcgcgt ggccgcggtc tccgccagcc gcatggggaa 86220 gtagaccatg tccccggaga tgagcacgtt cccgctagcg tttacgtagc tcactatctc 86280 ggacacggtg cgcagacgca cgatcgcgcc ttcgcagcag tgcaccacgt agtacccagc 86340 ggtggcgcgc aggcgcttgt tgtccgcctc gaagtccgcc tccaacccct cgttgaagta 86400 cttgtcgaat atgatgggca ggaaggatag ttttgactcg gtgaccacct ttccgaagtt 86460 gaggatgtac gggttcagcg cgctgcggtc gacctcttcg tcgtacacgc aggacttgaa 86520 ggtgtcggtg tgcgcctggc tgcgcaggaa gcagcacgga atgcagatgc gctgcaggcg 86580 gtggaagatg gagaggaagc ccacgctgtt gtagcgcccg tcggggtcca tgcacgaaaa 86640 catgacgccg tttccgttta cgaagacctc gcgcgtctcg gacttgaaga agttgttgct 86700 gaccttggcc atgttcgcgt ccagcgactg cacgatcacg ggcttgcggt tcttggtctt 86760 ggtgttctgg cagatgcgcg accagtacac ggtctccacc ttggtgaagt ccgaggactg 86820 cttcacgttg ttgaacatca cgctgatggc cacgatcaag aacgtgaagt acttctcgat 86880 gttcgggatg tagttcttta ccttcacgga cacgtgcgac ttcgcgagga tgatcgagat 86940 gcgcttgtcc gtggagagca ggatgttgtt ggtcgccgtc tccacgaaga tgaagctcgt 87000 ttccatgtcc agcttcatct tagacgtgat ggtcgtgttc agcgacacct tgtaggtgat 87060 gtcgcccttg acgcggtcca tctttacgtc catgctctcg atgagcttcg tgaacagact 87120 cacgtcgttc accgtgagcg tcttcccgtc gctcgagatg accaggtcgc cttccgggcc 87180 ccacaccgag aggttcagcg gctcgtccac cagcaggaag cgagtccccg tcatcgacac 87240 gaagaagtcg tccgtcttcg agagcaggat gtcgaagtcg cccacctccg ctcgcttgtc 87300 cggcgactgc tgcgcgatcg cgcggagccc ggactcgcgc aggttcgtgc ggaagatgtt 87360 gttgaacttg gtctccacgt tcatgtttag gtcgaggttc gcgaactcgc ggatgagccg 87420 ctcctcgaac ttgaggatgg agtcgttggg ctcctcgaag gagccgaact ccggcgcgga 87480 ggtgtccgcc gcgcgcgcca cccagaccac caggaagttg cacgcgtccg cgtacgcgtt 87540 gtagaggatg ccgtccgtgc ggatgagcgt tttcttttgc gtgggcgaga acgggttgaa 87600 gatggtgttg tccacgtagc tgtactccag gttgttcttg tgcgagtaca cgatgatctc 87660 gtcctgcagg cccagcaggc tccccaagta ccccttgagc tgccgcacgc gcatggtcag 87720 caagatgtgt ctgcgcacgt gctcggggtc cttctggatg tactgcttcg cgaagaagta 87780 gatcggcgag gcctcgtcca cggagtcgta cagcgatagg tacagcacgc gctcgatctc 87840 ctggtggcgc cccaccagca ccaccagctg cggcgcgacg gtgtagagca tgttcgcgcg 87900 ggcgtattta tagccggcgt taaactgaaa taaaatacgc gggtcgcgag gcagcgccat 87960 gttccagccg gtgcccgaca tggccgccga ggccgacatc gacctcggcg acgtcagcgt 88020 ggacgcgacg cgcgcgggcg cgcgcgagaa gaccgtcttc ttcgcgcgca acaagcgcat 88080 gtacccgcac cgcagcaagg acgaggagcg caagctgtcg ctgggcttct tcttgcagcg 88140 gctggacttc ctcacgtcgc gcgaggtcaa cctgcagttc cggtcgctgg acgcgctgcg 88200 caccgagaac gtcatgaaga agaacaacgt gctcgtggcg ccgtacatcc tcatcgcgac 88260 gctcgcgggg cgcggtttcc gcatgacgga gaccatggtc gagctctact tccccgagct 88320 gtaccgcgag accagcaagc gcttccgctt ctgcgcgcag ataaaggtca tccaggactt 88380 cctggggttc gcccacgaca gctaccacac ttacgacttc gagacgtact tcgcgttcgt 88440 ggcgctggtg ctgcgcggcg cggactctgc ggccgaggcc ttcgacgtcc gcgccgagag 88500 cgggcttgtg cgcagcctca ccgagatcac gtaccggctc tacgtgatgc agctgcgctc 88560 cgacgccgcg cagtggagcg tgagcaccgg cgccgtagtc tcgcaggcgg tgaacaccgt 88620 gctgtcggtc gtcggcgacc tcgctgcgcg cgcggaggcc gagcggctca cgcccgtgtg 88680 cgacctcgcg cgcgagaacc cgctctcgct cgaggacctg cgcaagtacg gcccgcggct 88740 gcgctcgctg ctcacgacca tggcgcgcgc gcgatccttc aagacgaacc ggcggggacaa 88800 ggacgcgctg tcccggttct gccgactgac ggcgggccct agcccgtctg cgtgccgcgc 88860 gtcgccatag gcgtcggcgc gcgctcgccg ccggaacact cggggtcgct gaacatgtag 88920 atgagcgcga cgcctagcag caggtacatg atcatgctga tcacggtttt gaacacgacg 88980 gcggcgaacg tgttggaccg cagtcggtgc tcgcagaagt gcatgaacag gtgccgcatg 89040 aggtcgatgg ccccgttggc cacctggaaa agggcgaggc cgccgatgga cttgatcacc 89100 gtcacgtagc acggccgcat tccgacgacg ctatttactc actgtcaaaa gaaacggcgc 89160 catccgaccg gaggttgagg ttgcgcttca tgttgttcca gtacatctca ccgatgctcg 89220 agtagtacgc cgtcagccgc gatatttttt ctcgcaccag ctcgtaggcc ttctgcatct 89280 ccgcaacgcc gatctccgcg tcgcccacgt accggccgct gcggcgcacg atcagcagca 89340 gcgccttcag gttctccagc gcgatcatgt ccatgtacag cgacttcgag agctgcacga 89400 agaggttgta ccgctccagg atgctgttct tcacctcgtc cgcgatcggg actccgaaga 89460 tgcgctccgt ggtgtacacg gactgcgtga gctgcttgaa gagcgcggag atgcagcagg 89520 tcgcgcgctt gacggcgtcg agctgcttct cggagcgcgc gctcgcgatg ctcagcgcgc 89580 tgttcacgac gttgctcgtg tcgcgcacgt agcgcgtctt cagcgcggcg ttgatggcat 89640 ccgcgatctc gttgctgctc acgctcgagt cgtccgagct gcccgagacc tcgtccagca 89700 gccccgagat cgtgatgtcg ggcgagccgc cgacggtcac cagacggtcg agcaggttgc 89760 agggcatgga catgaggatg ccctcgctcg agaggcagcc ctcgtcgatc atgctctgca 89820 ggttgcgctt gaaggccgtg ttttcgggca tgaacccgtc cacgctcatg agctcgtcga 89880 ccgtgctcgc ggaaaagatg cccctcacgt tgatgcggtc cagcatgccc atgtcctgcg 89940 agcacagcac caccgactgg tcggccgtct cggcggcgtc cttggcgccg ccgtagatga 90000 tgcgcggaaa ccgccagctc gccggaaaag agaaggaggg aaaccggcac tgcgcgctcg 90060 ggcctcggta gccctgcgcg tcgcgcacgt tggtggccgt gaccatgaac tgcagcaggt 90120 cgtgcgcgga cgccatgatc ttctccacct cctccttgct gcagcagacc ttgcccaggc 90180 tgcgcgcgat gttcgttttg ctcactgagg gcgagaccgt gacggcggtg tgtcggcggc 90240 tgccgagcgt gtacgcgctc acgctaacgc ggtaccccat ggcgccgaag agcagcttca 90300 cgaagtccag gtagctctcc ttattgatgt agtgcggcgc gcccttgtct tccatcctca 90360 gcccggcgta ggccatgagc acttccttca tcgccgtctc ggggtccgag ttgcacacca 90420 gccgcagcat ctggaagaac tgcatgaagg cgcgctgcga gagcccgatg tggtggttgg 90480 gctgcgtcga ccggcgcggg aactccctgg gcgtcatggc gttgatgccc gagagcgtct 90540 ccatcacgag cgcgcccacg gtcttctggc ccatgacgcg cgggtaaaag cacacgcgga 90600 ggggctcctt gccggccgcg agcgcgtccg agagcagcga gcagtacgtg acgttgtcgt 90660 ggtcgaagag cgcgaaggtg tagcagacgg agctcatgaa gagcgagtcg gcggtgctca 90720 tggacttgaa ctccgtgtac gcgattccgt cccagaacag gctctttccg ggcgcgatca 90780 gcggggacgc gcggtcggcg cgcatcagca tggagagcag cgtcacgtag taacggatgt 90840 tggcggaaat gtctacgaac tgcatgccgg gcgaggccac gcgcagggtc gcgcccgagg 90900 tagtgagcac ctccaggctg tccatgagcg tcacgctggg gtgcagctgc gcaaggcgcg 90960 ccagctggct ctggtagaag atggacacgg cgaggctggc cacgctgccg cgtgccatgc 91020 gcaggttttg cccgttgaag gtgagctggc gcagcgagaa cacggagtcg aagtactgga 91080 agaaggtgag caggtacttg agcggcatgg tcgtcagctc ggtatcccacc tgcggcgtct 91140 gtgcgagcac gattccgttc ttggccgcgg cgtcggggat gtcgtacatg gcgtccattc 91200 tggcgcggga ggcgtcggtg agcagcgcgc gcacgttgag cagcatgagc aggtcccgcg 91260 ctagcatggt cccgtcgacc agccgggcgc gaaagccgat ctcggcgggg ccggcgatgt 91320 tggggtagat caggttcagc aggtacgtgt tgtcgaagct cagcgagggg aaggagatgg 91380 gagacttcgc cgggaggccg gtggggtagc gcacgtagcc gccgcagatg cgcgcgtgcg 91440 cctcaaagct ggtcacgcga gtcttcagca ggttgcgggt gaagggcggc acgtccttga 91500 aggactgcgt gcagatcacg gggttggcgg tgtcggtcag cttgaggttg gtgggcttaa 91560 gctccgcgaa gttggggccc agcagcacgg ggacgaggtg cgagttggcg gcgctgtcga 91620 gcaggaagtt gatgccgaac tgcttcacgg cgacctcggt ttcctcgtcg ctggcgagct 91680 tctccgcgtc ctcgaggaag agcgcgtcca gcgggtgcac gtacgtgcgg ttgacgtcgt 91740 agctgggctt gaagtccgaa cacagcgtgg ggagcacggt ggagacgagc tggaacatgt 91800 attccgcgcc ctccacatgg tgcaaggcca tgtgcacgtt tggggccgtc atttatttag 91860 tattaaatga cggccgtacc ggtaaccgat attcctggag actacgggcc gacgtccttt 91920 tcggaggaca actacccgct gaacaagcac tacgagctca ccaaaggcca gctctcgatc 91980 ctgcgcacgg tcaacgacaa gctgctcgcg cgcaccgtgc agcactcgga cggggagagc 92040 gatgagagcg aaagcgagga ggacgacatc tccagtccgc tgccgccgga cgaggaggag 92100 ccggactcgt gcgtggcccg ggtcatgccg cgggacgcgg acctggcggc gccaaaaaag 92160 gccgacggct acatcattgc cgccgagcag cagcgccagc agcgcataaa cattctggta 92220 tccgatcgag aggccgtcgt ggagcgggag ccggttcaga cgtcgttcgc gcgcgtctcg 92280 gctatcccga tccacgggga cggcgcgcgc cgcaccaccg cctccttctc cgcgaccacg 92340 ccgtcgctgg gcgccgtgtt cgacgacgcc aagcgcgtgc ggctgctgga ggaggaggtc 92400 aaggagctcc gcagaaagtg cgcgacctct caggataacg gaaacctgga gaacttcacc 92460 aaggtgctgt tcggcaaggc gccgcgcgcg agcgagctga acaagcgcgt ggtcatcgtg 92520 aactacgcca cgctgaacaa cgtgacgctg tccatggagg acctcgagaa gtgctccgac 92580 gaggaagtgg accgcatgta ctcggtcatc cggcgctaca acgagacgcg gaagaagaag 92640 atcctggtca cgaacgtggt catcatcggg atcaccgtgc tcgagcacgt gctggtgaag 92700 cttggcttct cggaggtgcg cgggctcagc gccgacctct cgtcggagct catcgacgtg 92760 gagatcggcg aggactgcga gcacatcgcg gagcgcctgg ggttcgggaa cagcccggtg 92820 ctaaacgtgg cgctcttcgt ggtaaagctg ttcgtgcgga agctgaacct gatctgatca 92880 acacatgccg ccgtcgaggt ccatggcgtt catgaggttg gaggcgcggc ggcgcgcgcc 92940 ggtggaagcg gtggaggcgc tcgaggtcgt ggagcaggga gtgttgctgg aggaggcgcg 93000 gcggcgggg ctagaagcgg aactcgaggt tccgctggtg gtgctgcggc gactcgtgcc 93060 gctcgtgccg ctcctgctag tgccagtgcc agtgccgctg cggcgtgaag taccggtgcc 93120 ggacctgccg ctggagcttt tcttgcggcc gccgttaacg ctgtcgatgc cgagcaggtc 93180 ctcgcacacc tcgccgacgg ttccctgcac gtccaacttg ccgttcttga caaccccgta 93240 cacgatcttg ccgcagttgg acacagcctg gatggtggtc tcgtcgctgt caaaggcgtt 93300 cattccgccg cacccgccgt cgttgtttct tcgagaaggc gcgccgctgc ggcgactcct 93360 ggtgctgccg ctggaccgag ttccggagga cctggagccc gtggaccggc tgccggtcga 93420 cctggtgccg gtagtgcgct ttctggacga agaggaggag gcgcttccgc ggcgggtgga 93480 cgaactagcc tccagcgcac cggcgccgcc cacacaatcc acgtcggcgg cggcgcctcc 93540 gcgaatgacc tgctcgttgt tgagctgcgt caggagagat cgcagctgcg gcgcgatctt 93600 ctgcaaggtg ctcacgtagt cgtcgtagct gctctgcggg cgctgcgcca ttttttcgga 93660 cgccatttat tacgcggaat atctacgacg acgcagcact gaatcggttt ctcgcgacgg 93720 gagattccgc ggtcggcgcc ggtgcggggt tgtcaccggg cgacgaggta accagcgcgt 93780 ggaaggcgcg cacctggtcg tccgtcatct tgtcctcgaa cgaggacgcg cccgggggga 93840 gcaggtcctt gttgcgcgga acggcgggcg ccgagacgca cgaccggcgg tacatcatga 93900 tgacgatgta gcacacgatc gagatgacga tcacggtcag cagcgcgtcg aggagcccca 93960 tttattacct gtatatgccc gcgtttaccg ggcggtgagc tcaatgtcgg tgttgtttag 94020 ccgggcgtac gggacgctgc cggagcactt cctgtacatg ctgaacacga acagcccgag 94080 cagcagcacg gcgcccacta tgaagcaggt tacgcacagc gcgcgccaca cgtagtcggt 94140 gacgttgttg gtgttcttgc tgaaatccac gaaggcgaag acgcaggcgg ccgtcagcag 94200 cagcacgccg catatcagca ctccggagta gtaagagctc aaggtctcga atatgtccat 94260 ttatctgagg agaaatttaa attactgaat ggacgaagtg gaatagaaac cacgagaaca 94320 cgacggactg cagcacgaag atggtgctca gcttcgtctt catgggcatg cagaagttcg 94380 cggccagcgc catacagaag atgaacacga gcaccgccgg gtcgtagtcg gacaccattt 94440 acactacgct aaaaggcata tctcggcgcg cgacgtccac gagcaccagc acgcggacgc 94500 ccgcgggcgc gccggcggcg accgcggcga gctgcccggc cgtggggttc accagcagca 94560 gtgcgcgcgc ggttcgcggg acggggtctt cgtaggccat ggtcggcgtg gacccgggac 94620 gcagcggccg cccctgtctg tcgaagaggc cctcgggaaa cgaggtgccc ggaacggcca 94680 cgacgacggt gtcgctatct agaaacattt atggtcttgg tttccacgga tcgcctcgag 94740 tagaccgcca cgaagtagaa gatgacgccc gccgcgagcg ccgccaccag gaagggcggc 94800 acggcgggca ggttcgcgga cgcgttgtcg cgcacgccgg ggtccgggtc tgcgtagccc 94860 gcgcccacgg ccttgccgca gtcggcgatc atgtgcgcgc gcgagttctg catgaccagg 94920 ctgtccacgt cgatgcggca gcccacgtag cggcaccgcg agcgctgctc gtcctggctg 94980 aagaagagcc acttgcggtc gcgcgactgg tccgtgcact cgtgcgcgcg acagacgcgc 95040 gggcccaggt acttcccgag cgtggtgccc gcgacacacg cgcactccgg cgcggcgcgg 95100 tgcgcgtcgc agtagcgccg cagcgcggag tcgccgaagg cgaaggaggc gggccgcgcc 95160 acgcgcacga actccgagca gaagcgcgcg tccatgtgct tggcgcagag cgccgcgtag 95220 gtgtccagcg ccgcgtagcg gcccgtgcgc agccaggcca tgcactcggg cgcgtcaggc 95280 tccaccgcgc agcggctggc cataacgccg tcgcagtgcg cggtcttgta cccgttcgcg 95340 aacacggacg ggcacccggg ctccggattt gtgcagcagc gcgccatggc ggcgtccgtg 95400 ggcggcgccg aggcgccgat ctcgaacgcg cacatggtgc cctggcgcag gtacggcttc 95460 gcgatctcgg gaacgtagtc tgcgcgcagc agcgagcccg ggcggaagaa gagcgagtcg 95520 cagggcgggc ctcgcacgag ccgcgcgcgg ctcgccagct ctggcgagag gaagcgcccg 95580 cactgcccgg ggtccatggt cggcagcaga cagaaccgcg gccgtacggt cttcagcttc 95640 gggtcggaga aggtttctga ttcttccgcg aaggcgaagg tgtccgtggc gctcgtgtgt 95700 gtgacgcgca gcgcgtactc gcctggcgtc ggcgtgtcga gcacctccac cttggatacg 95760 gtgtccccca tttgaagacg ctatttacgc cgctgcctac tcggcgaaga ataggtcctc 95820 cgacttggcg cccgcgtaca ccgggcaggc gggcgcggcg gagcgagtgc gcacgatacc 95880 gcggccagtg aggcggaagg cgtagatggc gaacagcagg ccgagcacga tgtacatgaa 95940 agtggtggcg cccacagacc cggtcacgtg cgtcacgatg atggtgacga tggacatgat 96000 cgtgcacacg atggccatgc cggtgttgtt ggccgcgtag gggtgcatga tctgcatggc 96060 cgcacagtat ccgatgacca ggcacggcag cgggaggata agtgaggcaa tacctatcat 96120 tactagagcg agcacggggg tggacgtcaa ggccaataca aaaatcacaa tacctgttag 96180 tatgcggata tcctcgtact ggaggacgct gtaaggcgcg atattccctc cgggcactgg 96240 cctggggtta gccgggacta gggggggagtc ggcagtgccg gggtccttgg ggagaaaggc 96300 attctgctcc tccgggctga agagctcggc gtcctgaacg ccgccggcgg tgaactcgtc 96360 gttatagtaa ctaaagtagc tttccattta tatgttgaaa aatgtttgga ggcgtacagg 96420 tggacgacaa actctacgcg tacctaaaaa aactcgccgg acgcgggcgg ccgctgtgtc 96480 tgttccgcga caacggcgag ttcgtcgaag tcttcgcggg gtccgcgttc cgctttgtgc 96540 tgcccgtggg cctcttcgcg gacctgcgcg tgcgcacgcg cggcgtggcc ttcccgaaac 96600 tgcgcgactc cgcgcgcatg cgcggcgtgc gggtggacgc gcacacgctg ccctcgctgt 96660 accccaacca gcgcatcgtg gtggacgagg tgctcgcggc ccgcgaccag ttgctggccg 96720 cgggccgcgc cgtgtacgtg acgctgcatc tggcttgcgg cttcgggaag acgctgaccg 96780 cgtgccacct catcgccacg cacggccgcc gcgcggtggt gtgcgtgccc aaccgcatgc 96840 tggtgccgca gtggcgcgcg gccgtggcgg agctgcgggt gcccttcgcg gtctcctgtg 96900 acggcgcggc ctcgctgctg cgctcgggcg agctcgaccg cgccatggtg gccatcgtgg 96960 tcagccggca cttcgccaac gacgacttct gccgcgcggt gagccggcag tttgacgtgc 97020 tcgtgctcga cgagtcgcac acatacaacc tcatgaacaa caccgcggtc tcgcgcttct 97080 tgaccaagta cccgccgccc atgtgcttct tcctgaccgc gacgccgcgc acggccaacc 97140 gcatctactg caaccgcgtg gtgaacgtgt ccgtggtcag ccgcctcacc aaggtagtgc 97200 gcgtggtgga cgccttcttc gagccgtaca ccacgcccaa gatccgcacg ctcgagcgca 97260 gcctcgaggg accccagaac aagtaccacg tcttcaccga gaagatcctc ggcgaggacg 97320 tgcaccgcaa caagctcatc gtggacaccg tggtcgcggc catggccgcg ggcgaggcgc 97380 ggcgcgtgct cgtgctcacc aagctgcgcg aacacatggt cgggctgcac gccgcgctct 97440 gcgagcgcct cggtgcggag acggtctttc tcggcgacgc caagaacagg aagacgcccg 97500 aggtcacgcg cgcactgcgc gacaaggacc gcttcgtgct cgtgtccacg gtcttcttct 97560 cgggcacggg cctggacctg cccaacctgg acgcgctcgc ggtggccgcg gccgtgctca 97620 accgcatggt catggagcag atgatcggac gcgtgtgtcg cgagtcgcac gccaacacgc 97680 gcacgctgtt cgtgttcccg gactcctccg tgcgcgcgat ccgcgacacc gtgtctgcgt 97740 ttgcgcagcg gctcgtggcg ctggcggtgg acgggctggg cttcgtccgc gagcgcgccg 97800 ccgccggcgc gaagaacgag ccggcgctgt acagcgccat cagcgggcga gatctcgcag 97860 cggtgtaagc gcggacccgc acgccgcgca cgagagcgtg ctggagcagg cgagtcccag 97920 cgacagtgtg gacagcctgt ccacgtcctt gatgctcacc agccgcgagt tgcacgacga 97980 gcacacgggg tcgctactat catcgaccac cgtggtgacg cggcggcgtc tgcgcttttt 98040 gtttccagcg gcgacatcga ccacgcctcc cttagagccc cccttcgccc ccgccttagc 98100 tttcaccgcg ctcatctttt atttatcata aaaacacgtc tgcgtacgcg ttcgcgcaca 98160 cgtcccgcaa atccgcgcgc gcgccgcagc gcgtgaagcg cgcggcgtcc gcctccgcga 98220 tccgcgcgca cggcagcggc gcgcccttct cgtccgccat cacgcgcgca gagatcccgg 98280 tggcccccag cgcgtacgac accaccacgt cgccgacgca gcggtacacg ttgccggagc 98340 cggcgaggcg gtcgaacgcg gcgccctcct ggcgcagctt gtcgaatatg cgaggaacga 98400 ggatgttaaa aatgagaacg aaatagcaga tcagcaaaaa cagcgagatc atgacctccg 98460 agagcgattt atataccttg aaagagctaa tacgacttcg ggactcgctg cacctcgcca 98520 ccggcgccgc cgtcgagcgc tacaacgcgc tcgtggagtg ggccgcgcgc acgtactgga 98580 cggtcgcggt gctgccctcc gcgccgtgcg cctccatcga gaagtactac tgcgtgtgca 98640 aacccgactg cgcgctcgag cccggcgagt actccgtgag ccggctgcac ttcggactca 98700 cgcacgcctg ggtgcgcggc gccgccttca actcggccag cggcgccgag gtcgagccgc 98760 cagaggaggt gcgtagggcc tgcgaggcgc tcgacgccgc cttcgcggac ctcaccttcg 98820 tgcgcttctc ggtcttcggc cgcgagtgga cggtcgacga cgccgtcaca gaccactcct 98880 cgcgcgacga ggtgctcgcc gcgtgcgccg cctccggcgt gcgcgtcgcg cgcacgctgc 98940 gtgtgcgcgt gcgggcggga gagtccttcg cgcgcgcaga cttcgacgcg gtgcacgccg 99000 cgctgcgcgc ggagggcgac gtcgctcgcg gcaccgcggt ctgtctcgcg ctgcgcgggt 99060 catcgcgccg ctggatagcg gaccgcgcgc ctcgatgctt catgcgcgtg cgccgcgtgg 99120 agctcgagcc cgtggacgcg cggcaccact gcccggtgct gatctccgcg cgcggcgacc 99180 gggtgctctg ccgcggcgtg gggcacctcg cggacgcgcg cgcgcgcgag ggcgtcttcg 99240 tggccgtgcg caggtacccg gagtgtctgg tgctctgcga cgaggcggcc gccggcgcgg 99300 cggagtgctc gcgcgaggag gcgctgcggc tgctggtgcg ccgcttcggg cgcgacttcg 99360 ccgtcagcga ggagggctac gtcttccgcg tgcaggacat ggacttgcgc ggcgtgtccg 99420 cgcgactggg gctcgcgccc tgcgcgagcc tggaggagct gcgccgagcg gtggagcgcg 99480 accgcgcgct gatgaggcgg ctgcgcgcgg agggcgccgt gcgcctcgcg tgcgagtgcg 99540 tgggataccc gcgccagaac gcggtggagc tcataaataa tatgcgcttt caaataacgg 99600 aagaaggcgc ggtggcgaac tttgagctgg cgaacgcgag ctgtctcggc aacccgaccg 99660 cggagtccat cttcgcgagc ttcgcgcagt tcgtgccggt cttcaacgtg ctctcggcga 99720 tcgcgcgcgc gcagccatga tcgtggcggc cttcgacctt ggcacgcgca accccgcgcg 99780 caccgtgctg gaggtgctcg acggcacggt gcgcgtggtg gacgtggcca agctggactg 99840 gagccgcgac tgggagaagc gcgtgcaccg cgacgtgacc gccttccccg cgaacgtggt 99900 gctcgtggag cgccagtgca agatgtcgcc tttttctaag ttcatatact tcatacgcgg 99960 gctgctctac gacgggcggc gccgcacgcg cgtgctcgcg gtgccgccgg ccatgaccgg 100020 cagcacctac cggcagcgca agcgccgctc ggtgcgcacc ttccctcgcgc tcgcggagag 100080 cttcggcatc ctggacgccg tgcccgcgcg gaagaagctc gacgacgtcg cggacagctt 100140 caacatggcc atcaattacg tgctccgaac aaactgaaat acgactggaa cgaataagtc 100200 atgctggcgc tgttcgagtt cctgcggtcc gtggaggact gctaccggcg caccatcttc 100260 aacttccaca tcgcgcacag cgccgaggcg ggcgatgtct acggcgtgct gcgcgaccgc 100320 attttggcgg ccacgcgctt cgaggaggta gcgccgccag ggctcgcgga cgcgctggcc 100380 aaggtggtct actgcgacat aagcaccacc aagcacctgg tcaaccacgc ggccttcgcg 100440 gcgcgcgcgc ggccggcgcg gcgcggaggc agcctcgcgc agttcttcga cgtgcacgtg 100500 ggcgaggacg cggagagccg ccgcaccgcg gagatcttcg accgcgagcg ctcctcgctg 100560 gtctcgtacg tgaagaccac ggccaagcgc tgcaagatcg actacggcga gatcaagcgc 100620 accatccacg gcgggcggca gacctacttc tcggggcggc gctcggacga cttcctgagc 100680 accaccgtgc gcgcggaccc gagcaagccc tggatcaagt ccatctccaa gcagctgcgc 100740 gtggacatcc tgcaccacgc gatctgcacg cgcggcaaga gctccatcct gcagaccatc 100800 gagatcgtgc tcacgaaccg cacctgcgtg aagatattca aggactcgac catgcacata 100860 atcctctcca aggacgaccg cgagcgcggg ctcgcggacc tcgcggacaa gctcttcggg 100920 acctacgcga ccaccttccg cgtcatcgcg gccatcaccg gcaacgcctg cttcgcggcg 100980 gtggcggacg cggccgcgcg cgtggtcgcg ctcccggacg cggacgcgaa gctggcggcg 101040 gtgcgcgggc tcgcggagtg ctacggcgtg cgcaacttca aaatcggcat gttcaacctc 101100 accttcacgg gcgccatcga gcacacggtc ttcccctcgc tgatccccgc ggagagcaag 101160 atcaagttct tcaagggcaa gaagcttaac atcgtcgcgg tgcgctccac cgaggagggc 101220 cgcgagtgcg tggagcaggc gcaggcgctg ctcgcggcca tgcgcgagcg ctccgcgcgg 101280 ctcgcggccg cggacgtggc caccgcgagc gtggacttcc tcaaggagct gctggggcca 101340 tagtgaaata atactgattt cttaaatatg gagcaggcgc tcggatacaa gtttttgttg 101400 cccgacccca aggacgacgt ctactaccgc ccgctccact tccagtatga gtcatacgcc 101460 aacttcatca agcaccggct taaggacatc ctcacggtgc ggcgcacgct gctcaccttc 101520 aagaacggca ccgagtccat cgtgctcgag atcgacgacg tgaagatctc ggcgccggag 101580 ttctcgccca tcgtggccag catcaagggc cacagctacg aggcgctggt caccttcacg 101640 gtgaacatct accggcacgt gatgaccaag gacggcctca ccgttaccaa gatcaacagc 101700 tacgagggca ccgactcgca cctcgtcaag ctcccgctgc tcatcggcta cgggaacaag 101760 aacgcgctgg acccctccaa gttcgtggtc ccgaacgcca tcggcggcgt cttcatcaac 101820 aagcagtcca tcgagaagct cggcatcaac atgatcgaga agatcaccac ctggcccaag 101880 ttccgcgccg tgaaggccaa ctccttcacg ctctccttct cctcgatctc gcccgtgcac 101940 gtgatgcccg cgcggtaccg acactacaag atcctgctcg acgtgaacca gcccgacaac 102000 ttcgtgatct cctccgcgaa gaccttcatc accgtgaacg tgatcgtgat ggtgcagttc 102060 ctcgcggacg tcacgctcga gttcgtggcg cgcaacctct gcttcgacat gccgcccgag 102120 gccgcgcacc tggccaccgc gctcgtggag agcgcgaaga ccgtgcccgc gggcgcggac 102180 gtggccgagt acgtgaacgc gctcatcgcg gccgagcacg cgaagcagaa gtcgacgctg 102240 tccaaggagg agttccgcta cgagatgctc agcaacttcc tcccgcacat gcaggacagc 102300 gccaaccagc tcaagggcct gtacctgctc tcgctggtgc gcaagatggt cttctgcgtg 102360 ttcttcccga accggtaccc ggaccgcgac tcgctggtct gccaccgcgt gtacacctac 102420 gggcgctact tcgaggcgct ggccatggac gagctcgaga cctacatcgg gaacatccgc 102480 aacgacatcc tcgcgaacca caagaaccgc ggcacctgca ccgtgaacat ccacgtgctg 102540 accacgcccg gcttcaacca cgccttcgcg gcgctgctca gcggcaagtt ccgcaagtcc 102600 gacggcagct tccgcacgca cccgcactac tcctggatgc agagcatctc catcccgcgc 102660 agcgtgggct tctaccccga gcaggtcaag atctcgaaga tgttcaaggt gcgcatgtac 102720 caccccagcc agtacggctt cttctgcgcc tcggacgtgc ccgagcgcgg gccgcaggtc 102780 gggctcatct cgcagctctc cgtgctcgcc tccatctcga acatccgcac cgcggacttc 102840 gtcgagctca ccaagcgcgt ctgcgactac gtgcgctcct accccgcgcg cgacatcagc 102900 tacttcgaga ccgggttcgc ggtcaccgtc gagaacgcgc tcgtggcctc gctgaacccc 102960 gcgatcgtgg acgcgttcgt gctcgacctg cgccggcgca agcggctcgg cttcttcggg 103020 aaccgcgaga tcggcgtcgc gctcgtgcgc gaccgcatga acgaggtgcg catcaacttc 103080 ggcgcgggcc ggctcatccg cccgctgctc gtggtcgaga acggcgtgct cgtcatggac 103140 gcggaggcgg agcggctcga gcgcgacctc gccgcgatga ccttctcgga cgtgctgcgc 103200 gagttcccgc acgtgatcga gatcgtggac gtggagcagt tcagcttcag caacgtctgc 103260 gactccgtgc agcgcttccg cacgctgccg cccgaggagc gcgcgctctt cgacttctgc 103320 gacttcccgg ccgagttccg cgacgggtac gtggcctcct cgctcgtggg catcaaccac 103380 aactccgcgc cgcgcgccat cctcggctgc gcgcaggcca agcaggccat ctcctgcctg 103440 agcgcggacc tgcgcaacaa ggtcgacaac ggcatccacc tcatgttcgc ggagcggccc 103500 atcgtggtca gcaaggcgct ggagacctcc aagatcgcgg acaactgctt cgggcaccac 103560 gtcaccatcg cgctcatgtc cttccgcggc atgaaccagg aggacggcat catcctgaag 103620 cggcagttcg cggagcgcgg cgggctcgac atcctcacct gcaagaagta ccaggtcgag 103680 atcccgctcg agaacttcaa caaccgcgag cgcgtgcgct ccgcggcgta ctccaagatc 103740 gacgtcaacg gcgtggtgcg cctgaacgcc ttcctcgagc agggcgacgc catcgcgcgg 103800 aacgtgtcct cgcgcacgct cgacgacgac ttcgtcgccg acaaccagat cagcttcgac 103860 atcgcggagc ggtactcgga catctacgcc gcgcgcgtgg agcgcgtgca ggccgacctc 103920 accgacaagg tcaaggtgcg cgcgctgacc gtgcgcgagc gccgcgccat cctcggggac 103980 aagttcacca cgcgcaccag ccagaagggc acggtcgcgt acgtggccga cgagactgag 104040 ctgccctacg acgagaacgg gatcgcgccg gacgtgatca tcaactcgac ctccatcttc 104100 tcgcggaaga cgctctccat gctcatggag gtcatcctca ccacggccta cgggcacaag 104160 cccttcgccg aggacggctc caaccgcccg atctgcttcc ccagcaccaa cgagaccgac 104220 ttcgagacct acatcgagtt cgcgcggcgc tgctacgcgc tctcgcaccc cgaggccgcc 104280 gcggacgacc ccgagttcga gcaccgcgtc ttctgcgagc gcgtgctctt cgaccccgag 104340 accgacgagc ccttcgcggc gcgcgtcttc ttcgggccgc tgtactacct gcgtctgcgg 104400 cacctcacgc tggacaaggc cacggtgcgc tgccgcgggc gcaagaccaa gctcatccgg 104460 caggccaacg agggccgccg ccgcggcggc ggcatcaaga tcggcgagat ggagcgcgac 104520 tgcatgatct cgcacggcgc ggccttcacc gtcgccgaga tcctgcgcga ctccgaggag 104580 gacgcgcagg aggtgctcgt ctgcgagaac tgcggcgaca tcgcggcgcg gctcaacggc 104640 acgcacgtct gcatccgctg ctccaagatg agcctctcgc cggtgctcac gcgcatggac 104700 tccacgcacg tgagcaaggt cttcaccacg cagatgaacg cgcgcggcat aaagatccgc 104760 gtggagttcg agaagcagga cccctgcttc tacgggactc cgaaacggtt cagcctcgcg 104820 cccgacgagt cgctgttctc gccggaggac tgaacccgcc gtcgcgaccg cgtcgcgacg 104880 actagcttat cgttcgactg atgcgaaacg cgcggcggcg ccgcgactta gctttctcg 104940 actgatgcga acgcgcgacc tctcgcgact ttctagcttc tcagactgat gctaccatat 105000 cgcggcgtgc tggccccacc accagggctt ctcgccgtgg ctgacgcggg gctggctgcg 105060 acgcgcgctg cagtagctgc gcgcgcccca gtcgccgcgc acgtgcgccg ggggcaggct 105120 cccgtccagc gcgtgccgcg tcacctcggc gccgggccgg cggcacgtgt gcacgtccgt 105180 cttgttggag acgagcaccg cgtactgccg catggtctct atgtgatgct ccaagtgctt 105240 gcccgccatc cggttggact cgcagcacgt ttttgcttcg gctaaggttt tttctagagg 105300 ggatagtagc ttatccacgc gctcgggcag gacgcacgcg gagccgtcga accctacttt 105360 gaacggggtc accttgatgt tcccgtcgta gcggtcccac agcatcctga ggtaggttgt 105420 accgtcgggg tctgggtctg tccacactct aagcttttcg ctacagcggc cgtcgtacgt 105480 aagacggtct ctacgctcgt agtagtttct gcttatgttg ttggggtctc catgctcgta 105540 gtagtataaa tcgtacgcgc ctggcttttt taagtcgttt tcgtcgttgc tgacgtgtat 105600 cacgtcggga taataggata tcctaactgc actacaatct atagtatttg gtctagtaag 105660 ctgttcgaga tcaccttgtt catcatgatc tactgatttg tacacggcac cgtcgtgttc 105720 cgacggacgt atgaatatgt ccatggtaaa cgatgtaccc actttggaaa acgtatccca 105780 tgcagtaaag catagtccgt ccattataaa ctcaggaaca ctcataacaa atcgaaatct 105840 gtgaagtttt tcgaacacca cttttacatg gtctttgtca cgaacatcat tgccgtttac 105900 ttcagacatg aattgaagga acgctaaaga gtttcttgtt tcttcatgaa tctttccatt 105960 atacgtccat ccagtttcta gaattctata tatgcttttt gcatcgaccc cgtaccacca 106020 gtacatggga actccgaaat atatagctgg gtttgagtac caatgggcaa gagtgcccat 106080 tgcgtttaaa aagtcttgac aaaaaaatgc agtttttctg tcgataactt gacttggact 106140 acgttcgtgg acatcgtaca tgtccataat tggttcattg gtaacggtta catgacccgt 106200 cattatcttt ttaacaatca taagatacag tttgcctaaa gtcgaaatat gtataacgtt 106260 aatttttaca tgttctccta acgtaattgc gtttttactt agccattcgt cgtctacaaa 106320 aatcttacga tacataggat ttctctctac gtatcttcta aagtatagat ttaccggtct 106380 accggcgaca ttagcgccat ctatagcagg agcaagctgt atgtatcgtc gtataatgtc 106440 tcgtataagc tttctgtctt ctctgggaat acacgacacg gaacttagag actggtgcca 106500 gtgtctttca accaaagact tgaacctagc aaccaacgcg ttgtcactct ccatttataa 106560 ttaaataatt atcccaactt cgtatgttaa tccttattac cagatagcac cgctccttcc 106620 tctccaccac gtactatcta aaggatacct gtaagggtaa tgtctggata acgggcgtgt 106680 gagccaagac gtgttatggt gtcttcccca ccaacggtcc acttctctaa ctaccggagt 106740 gctagacgtt gtcgatccca ctactgttgt ttctccatta cctgtaatct ttgaagcgca 106800 acaagtgtta gtctttgcca aatcttctaa cggcttaatt aggtcgttaa gtctgtcaat 106860 atccatgcac tgaggtgtat cgttaccagt ttccccaact ttgggaggaa cttcctgttt 106920 agtgtccaaa taacccataa acctgtctct aagcattctt ctgtacgtgc ttttgtcatt 106980 gtctatgtct cccaaaaacc tgtgatttac gcatccgttg tacgtaagtc tgtcccttcg 107040 ctctcgctcg ttatttccta cttcttctat tgtactgtaa tgttgatagt ccaagtaata 107100 gccactgttt tcatgatttc ttgtaaatat aatcggtgtt ttatattga catcgtgttg 107160 cctactgtac gtatcttcca tggatctagg aacttgtcta gaaaattgag gactagaaat 107220 acgccttcca aatcctggat gataaaccaa acgcaatgca ctacagtcga catcgtcact 107280 gtctctagtt atcccatcaa caactccttc tttgtgatgc tccactgttt taaagttaac 107340 tcctctgtat atgttgagtg ttaaaaaaat atccacattg aacgcagttc catattttgt 107400 tattttatcc cacgacgtat aacacaaacc atccataatg aattccggaa ccgatactac 107460 aaaattagta tcgaacttat caaacgaaat gtttactcgc ggttgtgctt cgtatttttt 107520 gtcatacaca tctgtcatgt attgtacaaa atctatagct cctctagcat cgggcatgct 107580 aacgtctgga aaatcatttt ttaactgttc tagtacgaac tgttgatttt ggtcatctct 107640 ccaccagtac attggcaatc ctatcacaag agacttattt ttataataat ttgctacaga 107700 agctatatgc cacatgaaat tatagcaaaa ataatccatc tgtatgttta aaaccggttt 107760 actagtctgc tgagagtagc tatccatgat agtgtttccc tcgccaatac ttcctgacat 107820 tattctgtaa acaaccatta acaaaaatct tcctaccgtt gttatgttgt caaaagttct 107880 tatgttttga gcactttcga gtaaccatat gttattttca aatatacttt tgtaaactgg 107940 atttctgtcc acataactct ttaaaaatag atttactgga aggccgcttg ggttatctcc 108000 ctgtataggc ggcgcttgct ttatgtattc gcgtaacaaa tctcttacaa cttttctagt 108060 tcttctaggt atacatgacc tattattcaa aggctttgtc cagttagcgt ttataaacgt 108120 tgtaaagtca ctgactagct tctccattta taattaaata attacagacg gcaacacagc 108180 ggttatctaa tatctgctgt atcctgtctg tacatctatt tttctgttga gatcaagaag 108240 agctttacgt agactctcca agtgtctttc tagtctgtct aaccggttac ctgtttctct 108300 gcagcaatca gttatagttt tgtaactgtc taacaagctt acgaggcgct cttccacact 108360 ttctttagtt ggagctccag ccgcgtacac tccgttggtt gaattgcctg tatcatcagg 108420 ctgagtcaat aggttttctc cgtcattttc atccatattg agtccaacga acacaaacga 108480 gtaagtgttc ctctatttaa agtattgatt ttagaaaaag gcaagcctcg ctgccctgat 108540 tcggcggcaa acacgggttg aacacgcgga agtcgctcgc ggccgtgaag atctcgtccg 108600 cgcacgcctc cacgctcgcg aagcgcccag gcgagacgcc gtcgtgcgag cggaacccga 108660 actccgaggc cgccaccgcc gcgcccttga agagcacgca gcgccacttc ttgcgcacgt 108720 cgaaggcctc gtcgttgggg tcgaacacgc gccggtccac gcgcgggccg cccgccgtgc 108780 gcgcgaactc cagcgccgcg ttcgccgcgt tgaactcgcg gatgttgtcg tagttctcgt 108840 agacggccca gagctgcagc gccacgaaca tggcggccgc cgccgcgagg gccacgcaga 108900 gcgcggacac cgcgtccatc ttttatgtgc agaattattc gttggcgcgg agctcgcgca 108960 gctccgcggc gcgcagccgc gcgaaggctg ctttgagcgc gcgcagcagc tcctcggtgt 109020 ccgcgcgcag catgtcgaag cggtggtagc tgtccaggcg cgcgcggcag ccgaagaagc 109080 gtgcgacgca cgcggtgacg atgtcgttca cgtagagcac gcccgaggcc gtgcagtaca 109140 cggagcgcgg ctcgcgcggg tccggcggca cgtccacggc gaccgcgtgc gcggccacgt 109200 cctcgagcac cttgcgctcg agcacggcga ggaagtcgcg cagctggcgg cggttgtcca 109260 gccagcgta ggtggtcgcg aagagcgtga gccgcccgcg cggcgcgatc gcggtgtagg 109320 gcgcgtaccc gcggaactcc cgggggtgca cgaccttgac gttctcgtgc tcgcgacgga 109380 aggcctcggt gtcgagcagc gccgcgagcg cgtccacgag cttgtcggag acctccacgc 109440 ccgcgccgaa ggcgatgagc tcgatcttct gctcgctctt ggggcggaag tcgtggaagg 109500 tgtgcagcag catctcgcgg agctgcggcg gcttctcgac ggcctcgagc gcgtcgccgc 109560 ggacgaggaa gtagtcgagg tcgtgcagcg agacgtgctg cccggcggcg ctctgcacaa 109620 acttgaggaa gacgcagagg cccgcgcggc gctcgagcac gtcctcgacg tgcgcgtgga 109680 atacgtgccg cgagggcatg gcctcgatcg cggagagcca ctcctcgttg acgcaggtgg 109740 tggtgttctc cagcaccacg ccctgcgtga gcgcgggcca ctgcaggtgg aaggcgaact 109800 cgtgcttgat gagcgaggcc acggccgggt ccaggtccac ggccagcgcg gcctcgccga 109860 cgaggggagc gtccgccatc acgcggagga cgcctggccc atctcctttt tcgccttttt 109920 attcaggatc attattcttt cgttgacgag gtccatgagc atcttgatgg cggcggccgc 109980 ggccgccgcg tcgccgccgc acatctgcgc gatgcgcgtg agcatgtgca gcagcgcggc 110040 ctcgtttagg tcctcctcca tttagaggcc gtgagggcgc gcgtcgtcgc gacgagggga 110100 cgcctcccgc ggcagcgtgg tgcgcacggc gaaggcgagc agcgcgccgg cgcactgcgt 110160 gagcacacac tccgcgagcg cgacgaggag ctcggagggc gcgagcacca tttagaggcg 110220 cgcgcgggtt taattgccgc cgtcagagtc ggcatcatcg cccttgtcgc cgccgtcctt 110280 gcagtcgccc ttggtctcgg cgtcgacgat gtcggcgagc cgcgtcttca tgtgcgagaa 110340 ctgcgcgagc aggatgccgg ggtcgagaca gcgcttgacg acgctctcgt cggcgaagtc 110400 gtagcagatg cgctcctggt tctggcagaa caccgagtct tcgatgatca acaccctcct 110460 ggtcccggcc gaccgcatga tggccatggc ccggatgagc ctcttcttcg atccgcgtat 110520 ggacatggac cggagcacgt tctccacgtc ggagtcggag acgttgcagc agcagaggtg 110580 cgtgatgctg gcgcgcccgt tgacggggat gtgcttgtag gtctggcaga gcagcaccag 110640 cgacacgttg atggccgcc cgtagttcat gaggcccaag agtgtgggcg accgcgtctg 110700 cgtgtcgccc atatcgtcga gaatgatgag gaacttctgc ttcttcgtct gcgcgtgccg 110760 ctcgatcttg cgcttggcga ccgagaggtt gtactcgagc tcctcgtgcg tggtgacctt 110820 gtggatgtgg tccggccaca cgaagccgtc gtaggcggcg ttgtagacgg gcgtgaagag 110880 caggatgtgc ttgaagcggc gcacgagcgt gcggaagagc gagagcaggt aggcggtctt 110940 gccggagccg gagccgccga cgagcgccat cctgaagggc gcctcgatga gactctcccg 111000 cttgaagcgc acctcctgca cgacatccat cgtatattta ctgtcactaa attaccggct 111060 ccgagaaata tagaaattag agcctcctag agcacaccga ggcgcatcgg caagatggca 111120 cataacacgt tcgaaaacga tagcgagtcg gcagctaaca accagtacgt ggcgtcagtc 111180 aagcgccaga aaatgattcg gcgatacatt aagatgttct tccggttcgt tacggcgata 111240 gctatcattg tcctggctat tctagttgg attctgtcgc tatctctaga cgaatgtctg 111300 cacagagaac accctcatga ctattcacat gtacaaaatt caacatgcga cggcattact 111360 ttaggtggtg aaaagtgtct cagacttaat ttgccagcaa cgtgggaaga tgctaataga 111420 caatgtggta atcttgggtt ttacctacca tctactggcc ttgaaaagaa atttccttgg 111480 cttgtgacct atctcgacgg aacttgggga aacactcaga actccgtatt tggaccaacc 111540 ggtgacttgc agaatgtcat aggaccgaaa gaatacaaat atttttgtgt gtccgattag 111600 atgattataa tctaataaat gggttgctgt aaggtcccta accgccagtc tataaggact 111660 ttgaaaaagg cgtcctgtcc ggtcgccagt ctcgtcacca ttctctccct agtcaccagc 111720 ctcggtgcga tagtcagata caccaatttt tttctaaaag aagcatgtga cgaaggatgg 111780 atgcccataa aaaacatatg cattttaaac acgcactttg aagccaccaa tgacgatgcc 111840 cacaggatat gtgaaaacct agacggaaag ccgccggcca tccctaaccc tactctgtta 111900 aagggtgtca cagttctcac cggcgaaaag aaattttgga tgacccatca cgaagactat 111960 actactgtgt ttgagcatat agacgatagg acgactccta aaaacacaga ctatgacagt 112020 aaaaaacaca cttgtttgat gagcgaggac ggattgatac accataactg catgatgaac 112080 gtgactgtgg tatgcatgaa ggagatgcac ggataactga aaatatactg tttgaacgca 112140 aagacgccat gtcgcgactt caaatactga cctcatttgg acaaatcttc gcacccgacg 112200 aagctcggct gcgcgagatc gcgcgtgatt tgggaatatg caccataaaa cgcgcattcg 112260 gcgacatgct gtacggcttt atagacttcg acccggtgcc cctgacccaa gtaaacatgc 112320 tcatgtccaa ctgctacttc gcggtcaacg gcaacctgct tccgtgcacg gaggacttcc 112380 ggctcagact cccggcaacg gagatctctg cggcctacct gacgagaacg ggacggacga 112440 tcctgtgcgg caaagacttc aacatagtag cgccgtcggg gttcaagccg tccatgcggc 112500 tgcgcgacct cagtcacgtg tctgcgcttg tagagatcct ggaagtctac gacgagtccg 112560 ggggagtacca attcgtgctc ggccccagcg cgcagttcat gctgcggctg atggagaagg 112620 agaacgtctg tctgttcggc agcgggtggt gcatagtgga cctgcgcaag ctggacgtac 112680 ccatataatc agcatccttg tttttatcct gtctttttat cagtttttta gctagttaaa 112740 acataaatag taaagctaaa aagaggagtt ctggagtctt gcaacaacca ggatgaaggc 112800 ggtgttgttg ctggcgttac tgggagcgtt caccaacgca gcgcctttgt tagaaagcca 112860 gcgttctaac agtgaggaaa aagcaaattt ctgctcgacg cataatgatg aagtgtacgc 112920 caggttcagg cttcagatgc gcgtgggtgt acgacacagt ccgctctaca ctcccagcaa 112980 catgtgcatg ctggacatag aagactccgt tgaggacata gaagagtcca cagaaaaaga 113040 atacgcgtct acggccacgg gtgaggcggc cggagtgaac gtgtcagtgg cactagtggg 113100 agaaggcgtg agcataccgt ttagttacat aggccttgga ttcaacccgt cgcttgaaga 113160 tagctacctg tacgtcaacg tctcgtcacg agctccttgg gttaaacaga cttcggacct 113220 atccgcgaac ggcggctggg gtatcaaaca ggttctagaa aaagagttac tggccatcca 113280 aatagggtgc gacaaccaaa aatttcccga agaacccaca actacacccc cctcacctgt 113340 cactacaacg ctttcctcaa caactccaga tctgaatgaa gaaaacacag aaaatacgcc 113400 gacgaccacc ggcgccagtg tagacagaaa gcgcaatcca gctgacattg acttctcgct 113460 gctcgtggac ccccgatgcg tgacctctgt agacctgcac gtcgagctca gggacgcgtg 113520 catagactac aaacaagagt cgccgttgtc gctgaagggg aaatatggag acggcgaact 113580 agtaaaaaag gagattaaag acgtgggaaa gaatcacaat atgtgcagtc ttaacctcaa 113640 ccctggcaat tgagctgttt ttattcggca atataatagg tgattattga acattaaaca 113700 aaacttatcc cacaacgccg caacaatgga agtgctggtg atcatctcta ttatcgtcgc 113760 cgtaatatgc ttgaccggag cggtaatgta cctccttat gaactcggct tagccgccga 113820 gcgcgctaac aaacgcgcgc gcgtgaagaa aaatatgcgc aaattagcca ctcaattggg 113880 aaatggatct gtcgactccg gcataggcat aggcccgtgc ataatgtcgc gcaccatgga 113940 ctctggaccc agtcgctggg acagcgacag tgaggatgac ggggacagcc tgtccacgac 114000 gtccaccagc ggagggggga ctctcacccg agtgtgggtt gggagcgccg ggcctatgta 114060 cgaaaacttc tgcgggaacg gcacccgcca ctcccccacc aacgaccctg gctaccactc 114120 gcgggagact ctctgcagcg gacctccccg tcaggcgccg gcgctaccgc ccaccccgaa 114180 gcccgacgag gtaacggtgg acgtggggcc cggtcccgac gaccaacacg gtccgtacga 114240 ggaacctgat cccattcccc cgcaggaacc cgagccgccg gtgcagattg aggtaaccat 114300 caacgggccc ggtggagaag gcgaggcgga aggagaattt ttctacgacg agtagccgcc 114360 aaaactgaat aactatcggg cttcgtaaac gcgcagacat gccgctgttc cggaagctca 114420 tggtttcgcg ctccctggtc aaggaatgtc tgactctgga cttccggcag ggcgagcgtc 114480 tccctacgcg atgcttcctc ccggtgcccg cggggacgac attccacaga gtctgcgaca 114540 cctcgccgct gacggacgaa gtctcccggc acgtgcagga gcccgtcatg ggcaccggac 114600 gggtccagta ctactacttc gagagcggcc agggcatgat cggcgacaac gcgggcatgg 114660 cgcgcatgct cgtgtgcacg cggtcggcgt acaacggcgg cgacgtcgtc gtgcggtcca 114720 cgcggagcag agcagacaag accgtggtcg cgccctgcca gggcatggcg ctgctgctga 114780 gccccttctg cgccttcgac atcacgccgg tcgagagcgg ctccgcgata ttcgcggagg 114840 tcatcgtcac cgcgcccagc atggactacg tcgaggcggt caccggcacg ggcgaggcgg 114900 ccgtgcggat attcaactcg caccacccgc tctggccgcg acacggctcg aacgtctgct 114960 tcgcgctgcg gttgctgcga gacgtgcgca cgggcgagcg cgtggtcgag cagatgttca 115020 tggacgggcg ctggcacacc gtgctgagga cgtcctgcgg caacaaggtc tgcgtgcccg 115080 ccgacctcgt gggccagacg aacctcgagg aggtgccctt ctgcgacgtg acgcccgaga 115140 tcatgcgccg cgcgctggcg atcgacccgc cgtacgaggc cgtggcgcac ccgcaccgct 115200 gcgtgtacgg cgccatggac gtccggtgcg cgaacgagta cctcgtgtac tgcaccttca 115260 agacggagcc gacacggcgc agcacgtcct cgccgggccc ggacagcccg ctgtcgcccg 115320 cgactccgtc gacctcgcgg gccgcggccg cgcgcgtccc cacgacgccg caggaagtgg 115380 cctcgccgac cacgaggctc ctggagacct gtctgcgcga cgccctcgac ggactctgac 115440 ccgaaggacc caccgtccac tcacattcca ctgccagaca actcaagctt tttctgcatc 115500 tacctcgcta ataattgaat tgttatagga caaacaggcg cactcgagca caatggcgtg 115560 ttttatcgaa ttgttagact ccatcttcaa ccgacgccac cgtaatttcg ggccggagga 115620 catgtacagg ccctctgacg ccccgccccc caaatcgcac acgcctcgca ctccccgcac 115680 cccgcggacc cagtgtcccg gacacccgcg gcgacaaagc tcctctccca tctacggcgc 115740 ttatgtggac tccctgccga ggaacagaaa gcggttccag aatcaacaca gttgtcccgg 115800 agattacgag cggtgtcaac tctcggacac catcagcctg gatgcgacgc tactcacggt 115860 tacagtgacg tccatctcca gcatatccag ctctagtagc tcagactcta tctctctggg 115920 gcagtgcaga ctgtccatgg tgtccgcaac atcaacctcc acctccacaa ccttctcctc 115980 ctcggaatga gcgccacact tatttttgta taatagtttg tattgaacct tagagacatc 116040 cacaaatagt taggaagcat gagtagttca agtagcgaga ccacccctaa gcccaagccc 116100 atccctgctc ctcccatgac tcaggaggag tttaacaaag aagtgaagaa acgaaaagaa 116160 cagaaaaagg aaaaatctag aaccgttgaa cgtgagtcag aaaccgtaac tgtatcttcc 116220 gacggatcag agataaaaaa gacttacgag cgcgagtctg agagaacaac cgaaacagaa 116280 aagaacaaca cgtcaaccga tgataataag cagaacaccc ctgtagagaa accagaggaa 116340 accaagcctg cttctactcc tgaaggtgtg aagccagccg agactcctgc cccgactact 116400 gacccccaac ctactacaca accacccgca gaatcaaacc ctggaagtca acccgcacct 116460 gcttcagaac caacccccgc acctgagcct gcaccggaac ccactcagcc tgcatcagta 116520 actcaacccg ctccaacacc agagccaagt ccagccccta agcctactcc ggcttctgaa 116580 ccaaccccag catctgagcc tacttctgct ccagaaccta caccatccgc agaaccaact 116640 cctcaaccaa ctgtagaaac accaccatct gctccagcac caactcccga ggcccaacca 116700 cccgccaaca gcaatcccac tactgaaact accactggta ccagcacctc ctaagtgagt 116760 acgtaagcat ttcggagtaa cgtcgtagca agcgctagtc cgccgcgagc ggttctcgca 116820 agttttttcg ggtaaaaagc gtacaccgtc gccttgtcgc ggcggtgtac gcttttttca 116880 cgcccttttt gcaaaattta aattgtaccc gcgccggctc taggaaagat ggcgtgcctc 116940 agagtgttcc tggcggtgct cgcgctgtgc gggagcgtgc actcggcgca atggatcggc 117000 gagcgcgact tctgcacggc ccacgcgcag gacgtcttcg cgcggctgca ggtgtggatg 117060 cgcattgacc ggaacgtgac cgccgcggac aacagctcgg cctgcgcgct ggcgatagag 117120 acgccgccga gcaacttcga cgcggacgtc tacgtcgccg cggccggcat aaacgtcagc 117180 gtgtccgcga tcaactgcgg cttcttcaac atgcgccagg tagagacgac gtacaacacg 117240 gcacgccggc agatgtacgt gtacatggac tcctgggacc cttgggtgat cgacgacccc 117300 cagccgctct tcagccagga gtacgaaaac gaaacgcttc cgtacctgct ggaggttctg 117360 gagctagcga ggctgtacat tcgcgtgggc tgcacggtgc ccggagagca gcccttcgag 117420 gtgatcccgg ggatcgacta cccgcacacc ggcatggagt ttctccagca cgttctacgg 117480 ccgaaccgcc ggttcgctcc ggcgaagctg cacatggacc tcgaggtgga ccaccggtgc 117540 gtgagcgccg tccacgtgaa ggcgttcctg caggacgcct gtagcgcccg caaggcgcgg 117600 acgccactct acttcgcggg gcatggctgc aaccatccag atcgccggcc aaaaaaccca 117660 gtaccgcgcc ctcagcacgt atcgtcgccg atctccagga agtgcagcat gcagacggcg 117720 cgctaagggc gctcaccgcg ctgacggcgg ccgtggtgtg cgcgatcgcc atcgcgctcg 117780 agcgcggggc ggaggccgac gccgtggacc ttatccttat aaaattttca atgatatgct 117840 agtttttatg cgaccttcct tagaaaattc ggaattcaaa aatgaaataa aacggcgttt 117900 agcacgcata ttattaatac cgaccaccat ggcaggcgtc cgcagctgcc agaagaaagt 117960 cccttctact gcgggctcca tgtcatttca acggggcaac cggagcatcc agccggcgat 118020 gtccgaggcg ttgcagaatg atttcagcta caacccgcga ccgcctccgc cgagcgcaga 118080 agagattgac ttcttctgcg tggacatgcg caaagtactg atggaaattg aggccaagcc 118140 cagcagctcc aagtaccccg atttcatcac ccggttgaca gcagcccgcc gtgcacgccg 118200 gcgcgcaagc gcaacggctt cggccgcaag gcactgaaca aaacccaggt gccgcagcag 118260 gccaagcgtg acggctactc ccgctaatgc agtccacaca cttcacacac tacatcagca 118320 ctcaagctta taatcactac acaatgaatc agcccaccac gtgcgaagca cacacataaa 118380 atcacccacc tgtcctgatc gttcccaata ctcccaatca ccgtgcttta cacgcacgtt 118440 aatcaccctt tccttccttc atgcgttcct gatcgttcct cctccttaat cacacacaca 118500 ccccgtaatt ttgtactttt gtactttaat ttgtacactt tacacactga ctttgtactg 118560 cctttgtact ttatttttgt actgaaattg gacgatactt atctttgtat tcacatccaa 118620 gttttgcaaa ttccacagcc ggtagcgaaa agtgaaatcg taccgtttta ggcttcgatc 118680 ccccctcccgc gcgaagactc gccagcatgg actctcgtag gctcgctctt gccgtcgcct 118740 tcggaggcgt cctcgccagc atgacacagc gccgccgcct ggcttctctc atcgccagca 118800 tcggccaacg gctgatgggc ggcgacggca tgcgtcgcgt cgccgttcgg ttgatcgacc 118860 agctcatggc cggacccccg gacatcaacg acgaggcctt ccagcgcgag atccgcgtgg 118920 gcgagctctt ccaggcgctc caccgcgtgg tcgagcaggc acgccgagag aagtacttcg 118980 aggtctgcgg cgccggcaac gacgccgacg cgcccgtcgt cgagatggac accgcggccg 119040 cacccccgca gccccagccc gcgcccctcg tggtcacgcc gcagaacgcg ttcatgttcg 119100 tgccgcaagg cagccacgtg cacgtggacg agagcgtgga cccgttcttc ggcatgagcc 119160 cctccatctt cgggcgcgac ctcccccctc agccgcccga ggagctgctg agcgactacg 119220 acccgctcat gagccaggcc ggcgagccgc cgagcccgcg gtcgccctgc gaggccgacc 119280 tctggtgctt cgagacgctc ggcgacagcg acagcgattg agaccgcacc acaccctacc 119340 tcacccaccc cacactccac ctcacctcac cctaacaccc aacacccaac acctcaaccg 119400 gacaatgaag gagtcccaca tttcactgaa ggacgcggat gaagccgcac tcccccacat 119460 gaaggattgg caacggtcaa acatttcacc tgcaatgaag gacgatgcgc ggtcgcattg 119520 gcctgcgacc gacatcgcac acatgaagga cacaattggt ttgttaatcc ggacaatgaa 119580 ggacaaattg tttttgttaa tcaggacaat tagaacacaa tcaaattttt gtacgatcat 119640 aaaatcgata tttgatgcac atatattagt aagtatatta gactaaattc tccggggagg 119700 caagcagttg gatacggcgg ggcggggcac gacgtgcacg gagagttcgg gcgggtcccc 119760 cttcccccca cccccacgca ccacgatgcg cctaatctta gcgctcgtgg cctgcttgtt 119820 ggcggcgccg atgccgttat cgggtcgttc gacaagcact ccaaacacgt ccccctccgc 119880 actcggctcg acgagttcgg aaccaagctc ggaagacgct gtggcttcga gcacaacgac 119940 aagcacactc acaagcacta caagcacact cactatgtcc acaagtgtgg acaccactac 120000 tacctcgggc gctacaacgt ccgcaaacag cactcctgca gcgagtgtga gctcctccac 120060 acccgcaact accgaggcat cgacggcacc aacgacgccg tcgacgccga cgacagtgaa 120120 ggtaacgaag ggcaaggaag acacgaaggc gtctgcctac ctcgttttac taatcacgtt 120180 catggtcatg accacgctcg tgatggtcgt ggtcgtggtc gtggtcgtgt acaaacaggg 120240 actctgtaac tgctgctgta agtttccctg ctgcaaagag ctcaaggact acctcgacga 120300 ggaggagagc gccgggctgt acgacgcctt gacgtggagc cactcagact ccggcctccg 120360 gctcgtcgtg cgcgcggacc ccagatgatg aggatcggat aagatcggcg tgtttttccc 120420 gcccgtcgcg aacattatgc ctctaaatgc cgagaattaa ctgaaattca aacacgcttt 120480 gggactcaac tccgtgaccc acactcaacc atggctggct tcctaggcgc attcagaggc 120540 gtgtgctccg acttatggca gtcgctccgt ggacacggac accactcttc cagctgcccg 120600 cgacgacgcg ccaacagcat ggacgaccgc gaccggcgcc gacaccgcca ccgcgagatc 120660 cccaacagct cggcgtcgct gaacagcgac ccgatgccgc aacgcagtgc gggtgcgcgc 120720 cggcactacg actgccgccc ctcggaaaag agcagacact cctccgacaa gcaccactcg 120780 gcggaccgac accactcggc ggaccgacac caatcggcgg acagggacag acaccgtcgc 120840 agtcgcaaga actacgactc gcacccgtcg cgcaggaacc gcaactacga gcgggcggac 120900 taccagagac acccctcaca aacccaccca gacgcccccg cgcagacctc gacgctcaag 120960 gtgacctccc taagcaccag ctgcagcacc ctgtcccaac atcactacga gacccccgac 121020 cacatctacg acatcccgga agacagtcgc ggggcgtcgg ctccccctcg cgcggacctc 121080 gcgctccccc cgctcgccat gcccaaatcc aagccgcgtc gcacgcgccc ggcgtccatg 121140 aacgactgcc tgatgaagca ctgcggcgcc ggcagaccca acctccaaga cgacatatgc 121200 acactatgta ctgatataga gacacagctg agcgcactag agaagtctct ggagtcagag 121260 ctcaacttct atcgtcgcta catacaagac actaagacat tgctcgccac gcgagcagca 121320 aacatcggca gcaaagctct gatctacacc gacgactaca acggcagtgg cgacgtcggc 121380 gaaaaggagc actgctcgga ggagtgctgc aaagtggagg aagttctggg agaaagtgcg 121440 tttttctgta atgtgaaata agatagcctt atgtgtgcac agacatggcg aacaggctcg 121500 tgtttctcga ccccgagacc ctagccgagg ccgacggcat ccccggctat ggggtgttcg 121560 agcccggcaa gaagaaatgc atcttcacaa agatccgcac cagcgtcgca ctcgcgtgcc 121620 ggtacgccgt ctcggacggc ggcctcatcg acgagttcgt catggctaca tacgggacca 121680 gacgcgcgtg ccggctcgtc cggcacctga cgataggcgc ggagggcgtg atgacccggc 121740 ccgccagcaa ctgcgcgccg cacatggtgc tcatctgcct cagaggcgtg gccgccgtgt 121800 ccagcgagga catgggcttc ggtcgctgca tcatggagcg cggcaccatg ttcatggtca 121860 agtccgcgca cagcgccgtc gtctgcggca accccgcctg cgagctgctc gtcctcttct 121920 acgactactt cacccccatc ccccggccgc tctccggaga cgaggtgctg ttcacccgcg 121980 acctcgcgca cgtggactac gcccccgagt cggcggtcgt cttcaagatg gattacaacc 122040 tcgagaccga cgtggccacg ctgtttgtcg gggggtacat attccgcgcc aagggcctga 122100 tgatggagac gcgcgaacaa gtgggcgacg agtgcgactg ctgccgccac agctcgccgg 122160 tgctcgtcat ggatcgcgag aagatgatgt cgtcgctgcg catgatcccc agcatcgtgc 122220 ccggccagcg ggagatttgg cttcgcgagc gcggctgggc cgtcctcgag acggacgccc 122280 gcggacactg cgagcccggc gtcctgaggc tggcgctcgc cggcctgcgg ctgttcgcag 122340 gatgcctgcg ctccgtcgtg gggcggcgcg agctgtcgct gttctgctac ggcgtcgctc 122400 ccaagttcgg cggggagttc gaggacgcgc cgcgccccat ggagatcgac ggttagttgt 122460 ttttatccct gtacatacgc cgcaaactga aactttaggg caccgcgtaa tagtgcacga 122520 acgcccagtg gaccgcttcc gcagccatgg aaaacaacga cggcaacgaa cgcaacaacg 122580 aacacccgca cgttcgagaa ttcaaggagg cgtccctgta cgggtttctg gtggcggccg 122640 cggacgtgac cgtcgaagac gtgcaccggt accttcagtt cggcgcggac gtgaactaca 122700 ggggcgcgta cctgtgcacg ccgctgcacg cgtacctgca gtccggctgc gaaaagcgcc 122760 tagacgtcgt ggacgcgctg ctggacgccg gcgcagacat caacgccaag gagatctgcg 122820 gtctcacgcc cgtgcacctg tacgcgagct acgcggacgt ggacgtagag ttcatgcgcg 122880 ggctcatcga gcgcggcgcg agcgtgtgcg gcgagagctc ggtcacgggc tgcctgtact 122940 cgtacctgta cacacacagc gtggacggcg gcgcgcgcct ggacgtggtc gagctgctcg 123000 tgcaggcggg cgcggacgtg aacgtccgcg gcgaggcgcg caagacgccg ctgcacgtgc 123060 actgcgcggg cttcgaggtg gattcggaca tcgtggatct gctgctgcgc gcgggcgcgg 123120 accccgaggc gctcgacgaa cacgggctca cgcccgcgga cgtgctcgtg aagtccgtgg 123180 gcgccaacgt ggagacgctg cggctcttcc tcgacgcggg cgtgagcgtg gccacgtcgc 123240 gcgacgcgcg cggacgcacg ccgctgcacc accacgcaga ctccttccgg gcgagtgcgg 123300 gcatcgtgcg cgaactgctc gccgccggct gcgacgcggc ggccgccgac gacctcggaa 123360 acacgcccct gcacagcctc gccaccttct gctcgtgccg gcgctcggtg ctcgaccagc 123420 tcatcgccgg cggcgcggac atcaacgccc gcaaccacta cggccacacc tgtctgtact 123480 acgcgtccat ctacaacccc tccgtctgct cgcggctcat cgccgcgggt gcggacgtga 123540 ccgcgcgcac gccggacgga cgcacgccgc tctcgggcat gatcatgcgc aagcacacgc 123600 gcgccgtgcg cgccgccctg gcgacgcggc ctcccgcgga cgccgtcgcc gcgtcgctgg 123660 acgtcgcagt acagcccgag cccacggacg ccactcgcgc gtgcgtgcgg tacgtggtgc 123720 tctgcggcgg cacgctctcg gcgcgcgtgc ggtcgcgaca cgcggacttc gtgcgagagt 123780 gcgaaagcga ggtggtcgtg ctcagaacca ccgtggtggg gctgcccggc acctcgctgc 123840 tggacatcgt gcgtgcggcg cagccgccgc cggtactgct ctccccgcgc gtgcaccacg 123900 tgctgcagaa gctgtgcgtg tacgcggagt tggtggacgc gcggctgcgc gagatgcggc 123960 acaagaccaa cctcgtggac gcggtgtcgc ggctcgtgtg tccgtgcgcg ctgccgccgg 124020 aggtggtgcg cggcatcctc gtgcacgtgc cgatagacag cctgcggcac acgttgaccc 124080 tcggcgtggc gcaggcctcg cgtttccttc cctcgcataa atgaaatatt attttttgtg 124140 gtagaccgga tctccccgat ggaccccgcc ggacaacgac tgcgcgcgcc agggccgtgg 124200 cgcctgaacc cgccgaccgc ggccgcgctg gaaagcgcgc tgctgcggcc cgcggcgtcg 124260 gcgggcgccg accgctgcgc gaacgcgcac gtggaccgcc gcaacatggg cgtcggcgag 124320 ggccgcgagg tgcccgcgga cgtcgagggg ctcatgaccg agatccacct gcggtacgga 124380 atgacgcgcg tccaccggaa cgttcacttc gtgcagttct ggcacggcga gcacgtgcgc 124440 cggcgccccg cgcgacacgt gttcacggtc tggatctgcc tcagcggcga ggtgcgcatc 124500 tacgcagagt gctgccaggc ggggcacggc ttcgtgctct gccgacagat ggcggcaggg 124560 tacatgttcg tgaccgaacc cacggactcg gtcacggtct cggtgccgca ccgactgcgc 124620 aactcgcggt cgccggtgtg gctggcggcg gtcttcgcca cgcggcactt cgagccgctg 124680 ccgccgccca tgtacgccgt gcccgggcac gtggtgctcg cgcgcagcgc ctccatgctc 124740 tgcgactgct ggccgtcgga cccgcggcgc cgcaacgtga tcttctacat gcggctgtcg 124800 ggcgcgatgg tgcgcgtggt cgtgccgggc gcggagctcg agatcgagtg cacctcgggg 124860 ttccggccgg accacttctc catcaacgac gagtgcgtgt gctgcgagcg tccgcacgtc 124920 gcgcgaaccg cggtgtggac gctggcggag atttgccgcg gcgccacggt ggtgctcgcg 124980 ccgccactgc cccgcgaccg cgccgcgggg ctgctcgcgg agatccgcct ggcctcgctg 125040 cgatgggtgc gcgtgcgtgc ggtccgcagc ggcagagaaa gcgtgggccc gttcccctcg 125100 gtggtgtggg cggcggtctt ctccgccgtt cggctcttcc tggacggaac cgtgcctgcc 125160 ttcccggcgt gtgtggagaa tggacgcgcg gcgtacggca tggtgtacgt gcccccggag 125220 gagccgcgga tggacgggct ctgtgtgttc ccgacgcccg ccgagccggc ggcgctcttc 125280 gtccgcggag accaggtgct tgaggccggc gcggccgccg ccataatcgc ggccgctgag 125340 aagcgcgtcc aggccgccaa tgggtctcct gctgccgcgg aggaggacat aggtgcggcg 125400 gccgatgccg ccgcagagag cgtggagcag gaccagcgcg tcgagttcga ccttgggcct 125460 gggcctgacc ccagccaaga agcgcccgcg gacgcgcagc gtgccgattc ggacgacgac 125520 accggctccg agaccgagac cggcgacgag agtgtgggcg gcgaggatga cagcgactcc 125580 tcctcctctt actcggtgat gtcggacgac gaaaacgaca gcggcgacga gggctggggc 125640 gactctagcg actccggcat cgaggacgac gacggcggtg tcggccaggc cgccgaggaa 125700 gaagaggagg aagagcgcga cgtcctcggc gcagcggccc agatgctcgg agactgaccg 125760 gtggtgaaaa cataaaaata aactgttcaa cacttgtact ccgggcacca acactactat 125820 ccataccccac cctccctcca cacactacaa tggcaaacag agaagagatt gacgcctccg 125880 ccgtcatggc tgcctacctc gcgagagagt acgcggcggc tgtagaagaa cagctgacgc 125940 cgcgcgagcg cgatgcgctc gaagcccttc gcgtttccgg cgaggaggtc cggtcgccgc 126000 tgctgcaaga actctcgaac gcgggcgagc accgcgccaa ccccgaaaac tcgcacatcc 126060 ccgccgccct cgtctccgcg cttctcgaag cccccacctc ccccggccgc atggtcactg 126120 cgattgagct ctgcgcgcag atgggccggg tatggacgcg cggccgccag ctcgtcgaat 126180 tcatgcggct cgtgtacgtg ctcctagacc gtctgccgcc cacggccgac gaggacctca 126240 gcacctggct gcaggccgtc gcgcgcgtgc acggcacgcg gcgccgcctg caccgcgttc 126300 tcggcgtcgg ggccgtcatg gcaggcgtcg gtatgctgct gctcggcgtg cgcgtgttgc 126360 ggcgcacata actttttatc tcggctcaaa ctgaaatacg acattggact acgaaaccta 126420 tgattttgct cacggccgcg cgagatagga taataaataa cctttgagca actaacatgg 126480 ccgatgagag agaggccgac ggcgcgctgt tccggtacct ggagagcgag gaccgtccgg 126540 acgtggagca catgcgccgg ctgctggacg agggtgcgga cgtgaactac gcgggcccgc 126600 gcgggtacgc gccgctgcac atgctcatgc gcggcaaccc gctagacccc gacgcggtgc 126660 gactgctgct cgccgcgggc gcggacgtga acgcgacatc gctctgcggg ttcacgccgc 126720 tgcactccta catgtgcttc gggaccgtga cgccagacac gctgcgtgcg ctcatgcgcc 126780 acggcgcgag cgtcagcgac ctcgagcgca acatcaacgc gctgatcgag tacttcaacc 126840 gcgacggctg catgggcggc gcggaggcga ccgtgatcgc actgctggtg gagcacggcg 126900 cgcacgtgaa cgccaaagac gaccttggac gaacgccgct gcacatctac ctgtccggct 126960 tcttcgtgtc ggcaccggtg gcgctcgcgc tgatcgcgct cggcgcgaac ccgaacgcca 127020 cggacgcgta cgggcgcacg ccactgcacg ccttcctgcg ctcccgcgac gtggaccccg 127080 ctgtgctgaa gacgctcatc gccgcgggcg cagacccgct cgcgcgcgac atcatccggc 127140 gcacggcgct gcactaccac tgcgagtcct tcaagacgcg cgctagtgtt atagagacgc 127200 tggtggccgc cggctgcgac cccgcgagca cagacctgct cgacaacacg gcgctgcaca 127260 gcatggccat gggcagctcc tgccgcgcct cgctgatccg cccgctgctg gccgcgggcg 127320 tgtccgtgaa cgcgcgcaac gcgcggctgc agacgccgct gcacctcgcg gccgtgttca 127380 acccgccggc ctgcgcgcgg ctgctggccg cgggcgcgga ccccgcgctc gcggacctgg 127440 acgagacaac gccgctgctg agcatggtgc ggcacaactg cgcacgcgcg ctgcgcacgg 127500 cgctgccctt ggcgccggac gcgctggtgg ccggcgcggt gaaccgcgtg aacgcgcgca 127560 cgccgagcgc ggccacgcga gagtgcgtga tggcgctggc gctgcgcggc gcgctggacc 127620 tgctgagcgc ggagagcgtt gccacccacg cggccgcgat ccgcgcctgc gaggcggagg 127680 tcgcgctgct gcggcgcacg cgcctgggcg cgccgccgac gacgctcttc gcgctgctga 127740 caggacgacc gaacacgctg gtttccgcga aggcggcgcg acgcgcgatg gcggacgtgt 127800 gtgtctaccg cgcggcgctg gccgcgcgcg tggagcgcgt gcgccgcaag tcctcgctgg 127860 tcgagcgcct caccgccatg gtgtgtccgt gcgctctgcc gccagagcta gtgacgcgca 127920 tcctcgcgct cctgaccgtg gaggaactcg cttgcgcaat gcgcaaataa taatgaacta 127980 taactaggct tattagaggc actatttgtg cagagtcgtt agttatagtt agtgtactta 128040 caattggaat gtcgaagaac aaaattctgg tgtgttttgt aattattctt acttatacat 128100 tatacacaga tgcgtattgt gttgagtatg aggaaagtga ggaagataaa caacagtgcg 128160 gtagtagtag taattttcct gcgagtttac cgcacatgct tagagaactc agggcagcgt 128220 tcggaaaggt aaaaactttc ttccagatga aagaccaact gaacagtatg ctactcacac 128280 agtcgctcct cgacgacttc aaaggctacc tcgggtgtca ggcactttct gagatgatac 128340 agttttactt ggaagaggtg atgccgcagg cggaaaatca cgggccggac atcaaagagc 128400 acgttaactc gctgggagaa aaactcaaaa cgctgcgtct tcgactgcgt cgctgccacc 128460 gcttcctgcc gtgtgagaac aagagtaagg ccgtggagca agtcaaacgt gtgttcaaca 128520 tgctgcagga acgaggtgtt tacaaggcca tgagcgagtt cgacatattc atcaactaca 128580 tagaatcata catgactact aaaatgtaaa aatgtataca acttttagtt atcgttcgga 128640 ttctcgtatc gttctgcata ctatgtatat aaaatgtata ttaacatagt tacagttaca 128700 gttacagcta tatttttatg ctcacaagat gctatataat tgaaaggaaa ttgttcactc 128760 tctgtcaggg cgccatggac tttctaggcg ccgcgcttca cgactacgtt gccgatgcgc 128820 ccaaggtctg cgccgaggag gtgcggcggc tgctggccgc aggcgcctct gtggagtacg 128880 cgggcgagtt cgggaagacc gcgctgcacc agtacatggg ccgttccggc gcggaccccg 128940 ccgtcgtgcg cgcgctgctg gacgccggcg cgcgcgtgga cctcccggag acctgctgcg 129000 gctgcacgcc cgtgcacctc tgcctcatgg ccgccaatat cgacgtggag gttctccgca 129060 tgctcgtcca cgagggccgc gtcgaggact gcggccgcgc cgagctcgcc tccgtggtgc 129120 tcaaggagtt cgtggtgaac cgcgccttcg acgagaacgt caccgagcga gtgatgcgcg 129180 ttcttgtggc cgcgggcgcg gacgtgaacg ccgccagcgt ggtcgaccgc acgccgctgc 129240 acgtctgcct cacgggcatg tccacgcacc cgggcaccat cgccgcgctg ctgcgcttcg 129300 gcgcggacgt gaacgccgtg gacctctgcg gcatgtcgcc gctggcggtg ctcgtgcgct 129360 cgcgcgcggc gaccgcagag ctggtgcgca tgctgctcga cgcgggcgca gacgcacacg 129420 ctgtcgacag tcgcctggac tcgctgctgc accagcactt tcagtccgcg cgcccgcggc 129480 cggaggtggt gcgcgagctc atccgccacg gctgctcgcc gcgggcgcgg aaccgaatcg 129540 gcaacacgcc gctgcacgag gccgcaaaac actcctcctg caaacactcg ctggtggggc 129600 cgctgctggc tgccggcgcg agcgtggacg cgcgaaataa cacgggcagg acgccgctcc 129660 acttggcggt ggcgtccaac ccgcgcgcgt gccgccggct gatcgcgctt ggggcggacg 129720 tggtcgcgcg cagttacgcg ggcgtcacgc cgctggcgca gctgatcgcg gacaataact 129780 ccgcgctggt gaccgcggcg ctgaacacgc agcccgagcc gcgggccgtg gcagagtcgc 129840 tgcgagcgac cacgcccgtc ggcgagacag cgtgctcgcg gctctgtgg gcgtacgtgg 129900 tggcgcgcgc gccgagcgag gtcctcggcg agcccgagcg cgccctgcac gcggccttcg 129960 tggcggagtg cttagcggag gtagcggcca tacacgccgt gcgctgcggc acacctccgg 130020 tctcgctgct ggagatcctg gtggccgcgc gcccgccgcg gagcctgctc tcgcgccgcg 130080 cgtggcggct ggccagccgg acgacagttt accgcgcgcc gctccgtgca cgcatcgcgg 130140 ccatgcgcca tcgctcgcga ctggtggagc gcgcgctgcg cacgctgcgc ggctgcgtgc 130200 tcccgcgcga ggtgctggag cgcgtgctgc ggtgtctgtc cacacaggac ctgcgggcct 130260 ccggactggc cgagtagctt tttctgagat aagtgaataa acatggtggg attcgatcgc 130320 gccgccaacg ccacgccatg gacgccgccg agatggagga tctcgacatc aacgcggagt 130380 cggcgctgta cgactacttc atcctgaacg cggacagagc ccgcgtgggc gaggtggtta 130440 tgcttctcgc acagggcgcg gaaataaact acgcggacag cttcgacaag acgccgctgc 130500 acctgtactt gcacacgcga cacccgcgct cggacgtgat tctggcgctg atggaggcgg 130560 gcgcggtcgt ggacacgccg gagcgctgct gcggcgcgac cgcggcgcac ctgtacatcc 130620 tcaacgcggc caaggtcgac ctgtcggtgc tggaggccat gctgacctgg ggcgtgcgcc 130680 agaacgacca gcactcggag cggctgctct cgagcttgtt gcgcgagtac gtggtgaccc 130740 gcgcctactc ggatcagacc gagccgatca tggacttgct catcggcatg ggcgccgacg 130800 tggacatgcc ggtcggcgtg agtcgcacgg cgctgcacgc ctgccttacg ggcctgaacg 130860 cgaacccgtg catgattcgc gcgctgcttc ggcgcggcgc cagcgtgacc gcaaaagaca 130920 cctacgagat gacgccgctg gcggtgctgc tgaagtccgc gagcgcgacg ccggagctcg 130980 tgcgcatcct cgtggaggca ggctccgacg tgagcgccac cgacttccgc ctcaacggca 131040 tgctgcacca gcacgcgcag tccacgcgcc cgcgcgcgag cgtcatgcgc gagctcatcc 131100 ggctggggtg cagcccagcg gccaaaaaca tgtttgggaa cacgccgatg cacatgctgg 131160 ccatggaaag ctcctgccgc cgctcactga tcctcccgct gctggaggca gggctttccg 131220 tgaacgagga gaacccgcac tacggcaccg tgcctctgca cgtggcctcg gggtacgaca 131280 acacgcaggg ctgcctcaag ctcctccggc atggaggaga ccccaccgtc gtgtcggccg 131340 ccggacgcac gccgctctcg aacatgctcg tcaaacgcaa ccacgtggcg gtcgccggcg 131400 cgctgtcgac gcacccgagc gcggcagtag tcgtgcaggc tctcgagcag gctctcgaga 131460 acgtgctgaa cgccgggccc agcgaggcct cgcggctcgc cgtggccttt gtggtggcgc 131520 gcgccggcgc atccgcgcta ccggaggccg tgcgccgtct gcacgagggc tttgtcgccg 131580 actgcgagcg cgaagtcgag ctgctttccc gcaccatgct cggcacaccg gccgtgagcg 131640 cgctggtcgt gctggtcagc aaggaggtct ttggcactgt tatctcctcg cgtgcgctgc 131700 gcgtcgtgcg ggaggtccgc gtgtacgcaa ggccgctccg cgaggcgctc ataaatctgc 131760 gccacaaatg ccgcttagtt tccagcctta aaaggcaggt gggaccttgc tcgctgcccg 131820 gcgaactggt ggagcgcgtg ctcgcgaccg tgccactgac cgacttgcgc cgctcgtgcg 131880 gccgccgcgc gcccgagtaa ctgcccgtcc cgttgctacg cgactcgaga ctgcccgctg 131940 tttttctttc cccgtttctt cttattagga gttgttgccc gcctccatga tcctcgcacg 132000 cgccggcggg caacctcgca cgcccgcggc ggccgcggcc gccgccgagg acggcgagca 132060 cagtgatcgc cggaagcgca agcgcaagac gcccaactgc gaagacgccg acaactccga 132120 cgacgagcta gcgcagacgc cgtgcgaccg cgagtggccg gactgtcgcg cgagctcgat 132180 cacgagctcc gactcggtct ctctcggcga cgagatctac ctgcgatacg tggcctcgca 132240 ggtggacttc gcgcagacct gggccccgcc agtgcggctg ctgcgcttct tcgggaactt 132300 ctcgaaggaa acgctcaacc gcatgtcgcg gcgcgggtac gtgaaccgct cctacttcca 132360 gatggcgcac gcgcgcttct cgcccaccaa cgacgacatg taccacatgg ccacgggcgg 132420 gtacggcatc gtgttccgct tcgaccgcta cgtggttaag tacgtcttcg agcaccgcaa 132480 cggcatgtcc gagatggacg cctctacgga gtacacggtg ccgcggttcc tgcgcaataa 132540 cctcaagggc gacgagcgcg agttcgtggt ctgcgcgctg gccatggggc tgaactaccg 132600 gctgggcttc ctgcactcgc tgtaccggcg cgtgctgcac acgctgctgc tgctcatgcg 132660 cgtggaggaa ggccagcggc cctcggtgga gatgtccaag aagccgctgc tgcgctggtt 132720 cgaggcgcgc aaggacagcg agtccttcgt gcgcctgatc tcgtacttct acccctcggc 132780 cgtgcagagc aacgtgaacc tgatcaacaa cttccaccac ctggtgcact tcttcgagca 132840 cgagaagcgc gcgcggtacg tgttcgaccg cggggccgtg atcgtgttcc ctctggcgcg 132900 cgggtccgcg gactcgatct cgccggaggc ggcggcggcg ctgggcttcg cgccgcactc 132960 ggagttcctc aagttcgtgt tcctgcagat cgcgctgctg tacctgaaga tctacgagct 133020 cccgggctgc acgaacttcc tgcacgtgga cctgaagccc gacaacgtgc tcatcttcga 133080 cagtgcgcgc gcgctcagcg tgaccgcggc cggcgcgact ttccgcttcg aggagcccgt 133140 gcgcgcggcg ctgaacgact tcgacttcgc gcgcgtggcc accatcgaga accgcaagat 133200 cgcgggcagc gtccgcgtgc cgcagaactg gtactacgac ttccacttct tcgcgcacac 133260 gctgctgcgc gcgtacccgc acatcgccgc ggaggacccg ggcttccacg cgctgctctc 133320 ggagctcacg gtctcgtgct cgcgcgggac ctgcgaccgc ttccggctgc gcgtgtcctc 133380 gccgcacccc atcgagcacc tcgcgcggct ggtgcgccgc gacgtcttct cccgctggat 133440 aaatgccgcc gcggacgccc ccgacgccgc cgcactctcc tgagcccacg cccgcggcgc 133500 cgggctcgct gtacgacgtc ttcctcgcgc gcttcctgcg ccggctggcc gcgcgcgcgg 133560 cgccggcctc ggccgcctgc gccgtgcgcg tgggtgcggt gcgcggccgc ctgcggaact 133620 gcgagctagt ggtgctgaac cgctgccacg cggacgcggc cggcgcgctc gcgctagcct 133680 ccgcggcgct cgccgagacg ctggcggagc tcccgcgcgc ggacaagctc gccgtcgcgc 133740 tcgagctggg cgtggacccc gagcacccgg agctgacgcc ggaccccgcc tgcgcaggcg 133800 agagcgcact cgcacagaac atcgacatcc agacgctgga cctgggcgac tgcggagacc 133860 ccaaaggccg ccgactgcgc gtggcgctgg tgaacagcgg ccacgcggcc gcgaactgcg 133920 cgctcgcgcg cgtggcgacc gcgctgacgc gccgcgtgcc cgcgagccgg cacggcctcg 133980 cggagggcgg cacgccgccg tggacgctgc tgctggcggt ggccgcggtg acggtgctcg 134040 gcgtggtggc ggtttcactg ctgcggcgcg cgctgcgggt acgctaccgc ttcgcgcggc 134100 cggccgcgct gcgcgcgtag ccgcgcaaaa tgtaaattat aacgcccaac ttttaagggt 134160 gaggcgccat gaagttgctc gtcggcatac tagtagccgt gtgcttgcac cagtatctgc 134220 tgaacgcgga cagcaacacg aaaggatggt ccgaagtgct gaaaggcagc gagtgcaagc 134280 ctaggccgat tgttgttcct gtaagcgaga cgcacccaga gctgacttct cagcggttca 134340 acccgccgtg tgtcacgttg atgcgatgcg gcgggtgctg caacgacgag agcttggaat 134400 gcgtccccac ggaagaagta aacgtgacga tggaactcct gggggcgtcg ggctccggta 134460 gtaacgggat gcaacgtctg agcttcgtag agcataagaa atgcgattgt agaccacgat 134520 tcacaaccac gccaccgacg accacaaggc cgcccagaag acgccgctag aactttttat 134580 ggaccgcaga tccaaacgat gatgcgatca ggtcatgcgg aagaaggcgc cacggagcaa 134640 agtgaaaaag gaccgcctag cagtcgagac cctcccgccg cagccgcgga caccccacac 134700 ccgccttcca cccgccagac gccaacaccg cagccaacaa gcatgcaccc ctcgccgcgc 134760 aggctgctcg gcgcgctcgc gctggtggcg ctgggcttcc tcctcggcgg gctcttccgc 134820 cccgcggcgc cgccgctgcc ggccgccctc gtggaggcgg gccccgtccg cgcgaacggc 134880 tccgcctcgg tgacctgcct gaccgtcggc ggcgacgggc ggcacatggc ggtggtcgcg 134940 cacggcggcg ggacgctctc gccggtgtac ccgctcgccg ccggcatgca cgcgaccttc 135000 gcctcgctgc gcaagggcgc gctgctgctg aacgtcgcga ccgtgcacat ctacgacgtg 135060 cgcgcgctcg ggccggagtt cgagctgacc tgcgtcgcgg tggcgggcgg ctacaacgcg 135120 gcctgggcgg ccgcgcggcc cgcggccgag tggcgccgcc agctggcgcg gatgcaccgc 135180 tcggagctgt gaccctctcc ctcccggtct cccatccgtt tttgtaatcg gccttagtag 135240 attagaccag catcccgcgc ccttgtccgc cgcccttcgc tcgctcacga gcgaatcagt 135300 caattgatta tttttatcgc ccgcccgctc actccggtaa gggaacgcgg ttaacccact 135360 cacgagaaca agcgaccgcc actcacttga ggtaagggaa cggttacggt caactcactc 135420 acgagaacaa gttgactcac tcctcgaggt agagaacgag agaacaagtg accgtactca 135480 ctcacgagaa caagttgacg caccgctcac cgaggaaggg aacagagaac aagtaacagt 135540 aaccgttacc tcactcgcca ctcctcggaa taatagaacg agagaacgag agaacgagtt 135600 aaccgttgct cactcgctca ctcggtgtga gagaacaagt aacgttgctc actcgctcac 135660 tcggtgtgag agaacaagag aacgagtagc tgttgctaac tcaatcaccc ctcggagtaa 135720 gagaacaaga gcagtcaact acccactcag tcttggatga gaggcagagg acgagttgac 135780 gagttgaaca gttaatcctc actcactcag agcgagagag cgagagaggtg gaggacgagt 135840 taacaagtca atcctcactc agagtgagag agtgagagag tggaggacga gttaatggtt 135900 aacagttatc accactcaga gtgagagcgg aggacgagtc aaccactcgc tcgcccactc 135960 cgagttagag agggaaccag tgcgagttaa cgcgcacacg agcgagagaa cgtaaactcg 136020 ctcgcgcgct cgctcggcta accgtcggcc tctcccaaaa ctcttcgtaa aactttcccg 136080 atgacagttc accctccaaa actttgtaaa actaaactgt tcggaggtcg gtctgctgcc 136140 tctctaactc tccgtaaaac gtttgtaaac tgtcggaggt cggtgacccg ctcaaccgtc 136200 cgcgaaaact tttcgcaggc agtgtctgcc tctctcggac tctccgcaaa cactttcgcg 136260 gaacctcgga gggtggtcga cctctctcca aactcttgca aaactttttc gcggaaccgt 136320 tggaggccag tcctccctcc aaactctttg taaaatcttt tcgaggccag tcctcctctc 136380 caaaacgttc cgcaaaatct ttgggaggtc ggcctctcct ctccagaacg ttccgtaaaa 136440 ctcttggagg ccgcccgcgg cacgcgaggc ggaggatccg gagggtgtcg acctccctca 136500 aaaactttgt aaaaactttt tataaaactt tccgcggaac ctcggagagt aggtcgacct 136560 ctctcaaaac tcttataaaa cttttccgcg gaaccgttgg aaggtaggtc gacctctctc 136620 aaaactctta taaaactttt ccgcggaacc gttggaggca ggtcggcctc tcaaactctt 136680 tgcgagaact cttcgcgaga actcttcgat aactttagga ggtcaggtcg acctcccaaa 136740 acttttgcga gaactctctg taaaacttta ggaggtcggt acctccctca aaacttttta 136800 taaaactttt cgcggaacct ccggagacgg gccgccgccc gcgaccgcgg gagcggagag 136860 gccgacctcc cgagacgttc cgcgttaccg tcggggtagg cgtcctctcg agaacgccaa 136920 aagacttcgt gcaaaaactt ttcggagggg cgcggagggc gggtcagctc ccgcgaactc 136980 ccgcagaacc ttttcgcgcg accgcgaagg ccggccgcct ctcccacact ctcaagagct 137040 tttcggagga gaggaagggc aggtcgcccc cacctccgac gctttgtaaa aacgtttacg 137100 cggaacctcg gaggcaggtc gcctccctcg aaaactcctc gcgaaacctt taaaaacttt 137160 ttgcgaaaac ttttcggagg atgtcggagg gcgggcggct cttccaaacc tccgcagaac 137220 cttttcgcgc aaccgttgga agacaggtcg gcctctctcg aaaactttta aaactttgta 137280 aacgcgttgg cgggaccgtc gcgggagagc ggccgcccgc ggcacgcgag aggaggaacc 137340 gttggaaggc agtcggcctc tcccgaaaac tttttataaa aacttttccg cggaaccgtt 137400 ggaggcaggt cggcctctct cagagtctaa aaactttttg cgggactcgg acggcgcggt 137460 cacccgacca cctgactcct gtctacccga ctacttgact tctgtttccc tgactcccga 137520 ctccctgact cccgactccc tgactcccga ctccctgact cccgactccc tgactcccga 137580 ctccctgact cccgactccc tgactcccga ctccctgact cccgactccc tgactcccga 137640 ctccctgact cccgactccc tgactcccga ctccctgact cccgactccc tgactcccga 137700 ctccctgact cccgactccc tgactcccga ctccctgact cccgactccc tgactcccga 137760 ctccctgact ccctgactcc agagcgaggt ctcgcggctg cggggtgccg cctccgcgga 137820 gtcgcgttcc cgcggacgcc cgtcctcgaa agcattcagc agttccagcc tctgccgtag 137880 ctcctcccgc aggaactcct ggtccgcgtt ctcgcggcag cgcggctcag ccgccgcggg 137940 agccggccgc cgccccggcg aagccgcgga tccgctgttc cggcgaaggc aggacagaca 138000 ttttttccag cccataaatt aaaaagaaca agaaattaca tgtgaaaaaa tttgaggttg 138060 atttatgac gaaacgttca actaaataca atcctaaaag tttttatcat catgataatt 138120 ttctgttgat tctttttaat ttatgggctg gaaaaaatgt ctgtcctgcc ttcgccggaa 138180 cagcggatcc gcggcttcgc cgg 138203 <210> 3 <211> 188455 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 3 ggtttaatat ttttgtgaga ccatcgaaga gagaaagaga taaaactttt ttacgactcc 60 atcagaaaga ggtttaatat ttttgtgaga ccatcgaaga gagaaagaga taaaactttt 120 ttacgactcc atcagaaaga ggtttaatat ttttgtgaga ccatcgaaga gagaaagaga 180 taaaactttt ttacgactcc atcagaaaga ggtttaatat ttttgtgaga ccatcgaaga 240 gagaaagaga taaaactttt ttacgactcc atcagaaaga ggtttaatat ttttgtgaga 300 ccatcgaaga gagaaagaga taaaactttt ttacgactcc atcagaaaga ggtttaatat 360 ttttgtgaga ccatcgaaga gagaaagaga taaaactttt ttacgactcc atcagaaaga 420 ggtttaatat ttttgtgaga ccatcgaaga gagaaagaga taaaactttt ttacgactcc 480 atcagaaaga ggtttaatat ttttgtgaga ccatcgaaga gagaaagaga taaaactttt 540 ttacgactcc atcagaaaga ggtttaatat ttttgtgaga ccatcgaaga gagaaagaga 600 taaaactttt ttacgactcc atcagaaaga ggtttaatat ttttgtgaga ccatcgaaga 660 gagaaagaga taaaactttt ttacgactcc atcagaaaga ggtttaatat ttttgtgaga 720 ccatcgaaga gagaaagaga taaaactttt ttacgactcc atcagaaaga ggtttaatat 780 ttttgtgaga ccatcgaaga gagaaagaga taaaactttt ttacgactcc atcagaaaga 840 ggtttaatat ttttgtgaga ccatcgaaga gagaaagaga taaaactttt ttacgactcc 900 atcagaaaga ggtttaatat ttttgtgaga ccatcgaaga gagaaagaga taaaactttt 960 ttacgactcc atcagaaaga ggtttaatat ttttgtgaga ccatcgaaga gagaaagaga 1020 taaaactttt ttacgactcc atcagaaaga ggtttaatat ttttgtgaga ccatcgaaga 1080 gagaaagaga taaaactttt ttacgactcc atcagaaaga ggtttaatat ttttgtgaga 1140 ccatcgaaga gagaaagaga taaaactttt ttacgactcc atcagaaaga ggtttaatat 1200 ttttgtgaga ccatcgaaga gagaaagaga taaaactttt ttacgactcc atcagaaaga 1260 ggtttaatat ttttgtgaga ccatcgaaga gagaaagaga taaaactttt ttacgactcc 1320 atcagaaaga ggtttaatat ttttgtgaga ccatcgaaga gagaaagaga aagagatagt 1380 tagtctagat atttttctta gtacaaaagt caatgtttta aaatatatgg acaagaattt 1440 gtctgtataa aaacttgtgt gaaattttgt accaaagaaa aaatgtgagc agtatcccta 1500 catggatttt actagatcat ttatatacaa aaaatattat acgatctacg ttttattata 1560 tgattttaac gtgtaaatta taaacattat tttatgatat acaattgtct ggtaacctag 1620 atgggcatag gggatgttga taagctcgac gagtatatgt tgttggacgt tattgtttaa 1680 gaaatagttg atgcatcaga aagagaataa aaaatatttt agtgaaacca tcgaagagag 1740 aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca 1800 tcgaagagag aaagagaata aaaatatttt atgactccat tgaagagaga aagagaaaat 1860 gagaatgaga ataaaaatat tttagtgaca ccatcagaaa gaggtttaat atttttgtga 1920 gaccatcgaa gagagaaaga gaataaaaat attttatgac tccattgaag agagaaagag 1980 aaaatgagaa tgagaataaa aatattttag tgacaccatc agaaagaggt ttaatatttt 2040 ttatgagacc atcaaagaga gaaagagaat aaaaatattt ttgtaaaact ttttttatga 2100 gaccatcaaa gagagaaaga gaataaaaat atttttgtaa aacttttttt atgagaccat 2160 caaagagaga aagagaataa aaatattttt gtaaaacttt ttttatgaga ccatcaaaga 2220 gagaaagaga ataaaaatat ttttgtaaaa ctttttttat gagaccatca aagagagaaa 2280 gagaataaaa atatttttgt aaaacttttt ttatgagacc atcaaagaga gaaagagaat 2340 aaaaatattt ttgtaaaact ttttttatga gaccatcaaa gagagaaaga gaataaaaat 2400 atttttgtaa aacttttttt atgagaccat caaagagaga aagagaataa aaatattttt 2460 gtaaaacttt ttttatgaga ccatcaaaga gagaaagaga ataaaaatat ttttgtaaaa 2520 ctttttttat gagaccatca aagagagaaa gagaataaaa atatttttgt aaaacttttt 2580 ttatgagacc atcaaagaga gaaagagaat aaaaatattt ttgtaaaact ttttttatga 2640 gaccatcaaa gagagaaaga gaataaaaat atttttgtaa aacttttttt atgagaccat 2700 caaagagaga aagagaataa aaatattttt gtaaaacttt ttttatgaga ccatcaaaga 2760 gagaaagaga ataaaaatat ttttgtaaaa ctttttttat gagaccatca aagagagaaa 2820 gagaataaaa atatttttgt aaaacttttt ttatgagacc atcaaagaga gaaagagaat 2880 aaaaatattt ttgtaaaact ttttttatga gaccatcaaa gagagaaaga gaataaaaat 2940 atttttgtaa aacttttttt atgagaccat caaagagaga aagagaataa aaatattttt 3000 gtaaaacttt ttttatgaga ccatcaaaga gagaaagaga ataaaaatat ttttgtaaaa 3060 ctttttttat gagaccatca gaaagaggtt taatattttt gtgataccct gaaaggaaat 3120 aggaatagga ataggaatag tgtcataatc gtatcacact attgagacag aaaaagaaga 3180 agtcgcgaga ggtaactttt tgtgaatgta gttaagaaca tttttgtttt gcaaaccgga 3240 atatagtgtc cggtacactt ttttaattcg tggtgtgcct gaatcgttcg attaacccta 3300 ctcatccaat ttcagatgaa tagagttatc gattcagaca cacgctttga gttttgttga 3360 atcgatgagt gaagtatcat cggttgcacc ttcagatgcc gatccgtcga catacttgaa 3420 tccatccttg acctcaagtt cagatgattc cttgcacatg tctccgatac gaacgctaaa 3480 ctctagattc ttgacacatt ttgtatcgac gatcgttgaa ccgatgatat cttcgtaact 3540 cactttctta tgagagatgt tagacccgag tactggatgg gtcttgatgt cgctgtcttt 3600 ctcttcttcg ctacatctga tgtcgataga cacctcacag tctttgatca tagcaagagc 3660 ttcttcatga gtgatcgcgg gagagtcctt accttgtcct ggggacacgc tggacaatct 3720 agcattcact gtgtttccat cagcggattc tgagatggat ttaatctgag gacatttggt 3780 gaatccaaag ttcattctca gacctccacc gatgatggag taataagtgg taggaggatc 3840 tacatcctcg actgatgtgg aatcatcttc tgattccacc tcgggatctg gatctgactc 3900 ggactctgta atttccgtta cggattggca aatcttatca ttggtcggtg tttggtcttg 3960 ctttgtgact ttgataataa catcgattcc catatgatgt ttgttttctt cttccgtaca 4020 cgaggaggag gatgaggatg attgctgaag actggcaggc atagcagctg ccgccaggca 4080 catgcatgcc agtacgatat attgtttcat aattgctatt gattgagtac tgttctttat 4140 gattctactt ccttaccgtg caataaatta gaatatattt tctactttta cgagaaatta 4200 attattgtat ttattattta tgggtgaaaa acttactata aaaagtgggt gggtttggaa 4260 ttagtgatca gtttatgtat atcgcaacta ccgggcatat ggctatcgac atcgagaaca 4320 ttaccacatg ataagagatt gtatcagttt cgtagtcttg agtattggta ttactatata 4380 gtatatagat gtcgcccact agagttactg tctccgaatg cggcatgata gtatcattct 4440 ttgctttcgt taactgtttg gaggaagaat ctttgttatt gcatttaatc tcgaaattca 4500 gagtgcacac ctttctcctg taaagaaacc tgaagtcgct accttattaa gaacggagaa 4560 gtatccatca cgaaagacgg gatcgcagtc tttatgattc atagtaatag ttagttccga 4620 cgttgagatg gattcgctga gaccggtagt ggtcgtccga gtacacgacg tgtcgttgac 4680 ggggatacaga ttaatttcca catcgatata gttaaaggta tttctgggta cgggttcgca 4740 tttatctgcg gaagagacgg tgtgagaata tgttccgaga ccacacggag aacagatgac 4800 gtctccggat actccgtatc ctattccaca ttttgtttgg gaaacacatg ccttgcatcc 4860 ggatgatcct ttgagaagac aataatatcc gggagagcat tcacagattc tattgtgagt 4920 cgtgttacac gatcgcgtct tccgttacaa cttagacaag cgggtaaatg attattgcga 4980 gatgtgaagg tacccgaacc acacggcgta catcgtgtgt tagtcttgct atcgcataat 5040 ctggaagcgt atgttcccgg acacaaatta tggcgtttgt attcgttgtc tttacacttt 5100 ccatcggatg gtgcatgcgg tgctatatct cttccgttta ttattataca tgagagaaac 5160 aatatatacg agtataatac ggacttcatg atttaataat gtagtaatcg tcgtcttgtt 5220 cctgtttcct acttctccaa tcatatagat attttctttc tatcatggat aatatttgta 5280 atggttcttt ccgtacaaca tactgtttag atgatattgc gcataatttc cggaggcaaa 5340 tacgatagtc tagattgacc gatggtagac tctaatttat tgagtgcttt gtcgacgagt 5400 ttacttttac gctccatcga tagatggcac tgttctatga gatcgtcgta catgggaaat 5460 gaaatgtgtc tgtctgaatg tatggcttta agatagctgt gataccgtat acaggtcggt 5520 gtcggagatt cgaatctctt taaggcgact tatgtcacga tgatggaatc tatcttatcg 5580 aatgatatat ttttcataaa tacactttta tagtcctcgt ttaaacagaa tttactatgt 5640 agttccgcga atgactcgtc ccttaatagg cagtaggcta gtatcttttt tacgtagtaa 5700 tcgtcgtagg gagagacatc ttgtagaaca acgatttaat cataggtaga gatactttca 5760 gtctgtggtg gatgatgtca ttcacaacat ccgccttgta tatgatgttt ctgttttcaa 5820 acaccaagtc gaataccgtc tttagtcgga aggttgatgt cgtatccgat gtatgaggca 5880 acattgttgt tacaattttg aaaggcggta ttatagtatt cgtctttctg aatgtcgaac 5940 ctatctaata gataccgtag tatattgaga gtgtatcctt gattatgttt tatgaataga 6000 taaagtagat gttgtccttc ttccttttgt tcgtgccaat tgagtaacat tatgagaata 6060 tgacctgttg cacaatcgtt ccatgatggg tgtacaatca agattattac gtatcctcga 6120 gataaaagag catacaccac acgaggacta tgtttggtat actgttgaag gtaagtgtgt 6180 aaccgcgtta atgtttgctc cataatctat tatcgcgtag atgaatcgct tctcggctcg 6240 catcttagtg tgacttgact tgtaataatt gctttcgtag aacgtggata tgtgtttaca 6300 gtagtaatga agagaagtga gttcatcctc gtcggcgcaa ttagggtcgg atcctttgta 6360 cagaacgtaa tagtttaagc tcccattgaa tttatatcta agataacaca gcaatagatc 6420 ggatgattta ctaaagtcat caatggtgtc cgttagtata tcaaagatct tgttatcgat 6480 tgatagtggt catccttgct atcaaagtta cgcatgccgt ggtgtaacaa tatctttaat 6540 acagatggat taaatcgtgt attcatcgta tagcaatgta atggagagtt acctcgttta 6600 ttcagatcgc agtgtttaat aactagctta aacagatgag acgatgtatc cacatcaaag 6660 aacgtaaaat acatatgaca gacattgttg acagaaacgt gaccttcatt cttaccgtcg 6720 tccataaata cgttaggtat aaaccacata ctatcgcgaa cgatgctcac aatctcgtcc 6780 atctcataat gatttacttt ttcataatta aagatgtgaa agaaaaacag aacaatatat 6840 ttttttagta atgtttatgc gagacatata aaataaactc cgtgtttatg atgccggtaa 6900 atgtttttat catcttggac ggaatcgatt ttgtaatatg tcatggaaac aaatgaaaca 6960 ggacattatc gctccatgat aaattattta atggagtaat aaagtatctc catgggtaat 7020 ttcgaaatca agttatcgtc tgtattaatg ttgtccacta tggagtcgat cctctcattg 7080 ttctttacag tttctgtaat gatggacgtt agttcttttt tgtaccattt gatgtcggat 7140 tctttgcgta tctcagtctg tggcgtttgc ttcgtttaaa gaatatatca aacatggaga 7200 cgcctgatat gtagacattc ttcattctat taatgtctgc tctatagcgc tttagttcct 7260 tatgacgacc ggagatatca tactttactt tagaaggaaa atcatcatct aggattaagg 7320 cgtatctgat acaggcgaat aatggttcag gatatagata gcgtatatct ctattaaatg 7380 cgtcaatcat agtctctaga gtgggatggt aactcagtaa taaatcaact atcctcgttt 7440 tgttttctct tctgtaactg cttttctgga tggccgtatt gattatcgag cgtttacttt 7500 agaaggaaaa tcatcatcta ggattaaggc gtatctgata caggcgaata atggttcagg 7560 atatagatag cgtatatctc tattaaatgc gtcaatcata gtctctagag tgggatggta 7620 actcagtaat aaatcaacta tcctcgtttt gttttctctt ctgtaactgc ttttctggat 7680 ggccgtattg attatcgagc gtgatgttgt aacactcgct ccatattcca ataaccgctt 7740 tgcaaattgt atattattga catcgaccgc gtaatatagt agagttatcg atcatatcta 7800 tatcatccat gtacttgctt agtatatcaa atacatctat cagtatggtt tcataacagt 7860 gatacccgca attattaaat ctcgataata tcagaccgta catacataga cggccattgt 7920 tcgatacgtg atttacagcc gcgtgtccat attttccacg ataaacctta cgacgtttac 7980 atcgacgaga ttattattaa caaagtagtc gtgcagagga tagttgttgt ccgttatcta 8040 acatgcatcg aacgaccata tcgccgtaat gtaagtagtt tatcaacatg gcttgtacat 8100 cctgttgtct aaatctcttt agaatgttat cgatgatgta gtggttatat tctctggaat 8160 cgtacgaagt aatactacgc attacgtcga caagagtatg acgtctctca ataagaagat 8220 taacgatttc catgtctaca ttatatgggg ttactctaaa tcgcttgttt agataatacg 8280 cctctaatat agggctgacg tcgtatactc tacacgtgtc cacatccttt attaataata 8340 atttaacaat ctctatatct atggttgagc aagaccagta gtattggatg ggtaaagatc 8400 ctccttcgtc tctgccatgg atggaaacat tgttatcgat caaacattta attacatcct 8460 tggatagaga ttgagattct ctatgagacg atatatagta atgaagagag ttcttacaca 8520 tatcactgtc gtacatacag gtacgaaata cgtaaccggt gctgtaacat tctgatttaa 8580 gaagccatag caatacttct ggtctcggat taggcgtcgt tacgtatata tccaccaatc 8640 cgagaccatt gattgcataa ttcgtattct tggacggacg tatccgttta tccacaatta 8700 ggtattttag cagacgtaag tcgatattat acgaatacag atcgaaatca tttatattcg 8760 acttgagttc gttagaggaa ttcgaatagc tggatatcag tagatgcaca atctgagatt 8820 tgacgtatct atgcttactg tatactccta gcggagttaa tccttcgttg tttctacaaa 8880 gtctctcgac tccgcgagag agtaacagcc gaacaatctt aatgtctgta tcgcatttat 8940 tgaagacgta acaatgtagc gcattgtttc ctcgtctatc tatatgtttt gataagttgt 9000 gacacgtttc aatctctggt tttattttt tgtacgtcac atcttcatcc agtagacgac 9060 atagaatagt gcactctcta ccacaataat ccatagctat tctggtgcta attattccta 9120 tttcacgaag gcaatcattc ctcataagat gataaaaagt gtagtgagag agcatgaagg 9180 agatttagta tttagcagtg cggatatgat ccaagagggt gagatagtcg ttctcgttca 9240 gaatctttcg cagcataagt agtatgtcga tatacttatc gttgaagact cttccagaga 9300 cgatagctga ttgagtacaa agtccaatga ttgcacgaag ttcttcggcg gttttcatgg 9360 agtcatttct gatgaaacat ttaatgatct ccacgcaatt gtcccacgga agtgaatcct 9420 tcaactcacc accaaagagc tccgttgcat cagttctgaa agagatgaga agcctgtaga 9480 gagaccctgc gctttctcta tgggtccatc tatgagaaac ccacaggatg tattcagtca 9540 gacaatgtct gacgtcggcc acggtattca gggagtcctt agtagcgtgg caatgacagg 9600 gactgaactt ggcacaagga aaggccattg tgaaggtaga cctgtagccg tttatgctaa 9660 tagagggctt taatttccat tttttaatgg gttgtggatg aggaatgaga gtgatatcat 9720 attgagatac gtagttatgt agaggtgtat ttcctatatt atttactttc ggtttcatat 9780 tttaccaact ctttaataaa tttcttttca cgatgcatct tattaaatga cgttttctca 9840 taagtggaca tatagatgca gaagtaatga agaaaagtat tacctctatc atctacataa 9900 ttagggtctg ctcctttttt taacaactta tacagtacgt agtagtagtt tatcggtttt 9960 aaatcaagtc tagaatatat agtggattaa tatattttta tattagctaa agctatctat 10020 actatcagaa agcatatcat tctcaacttc atcatgagtt aaatatttgt gtaatggatg 10080 tcatgaacat taaacgtatt catgacatac tcctttaata ggttttttaa aacagatgat 10140 tcaaatcctt cattcattag ataacagtgt aacggagtcg taccttctac tagtttgttt 10200 atatcacagc attctacaaa cagtctaaac aatagagaag acggacagac tttaacgtat 10260 aaatgacaca tgttatcgat attcgttgat gaattattat taaacgtagt tatgataaat 10320 gattctaacg acatctctcg ctagagataa aatctagtat cgtatcatac tcgcatagca 10380 tagttttca taattaatac aatatttaaa agacttattc agaaagtatt ttaatacatg 10440 tatcatcgat ggagatccat atgaggagtc acttgtagtt cttcagtagt aataacagtg 10500 ctatcatcga tagtataatt atatgttgtt gtaattggag taactgttgg tagttcttcc 10560 gtggaatcaa taattatact aacagcaata gtataattat ataaatatgt tccgttgata 10620 tcacatattt taatgaactc atttctaaca ccctcagcta tatctgtcca attaaatgta 10680 gccaacaatc tactacgttc tctttgattg actacttgta cggtagcgac gctacactat 10740 ctttatgtc ttctacatgc tccaattgaa tgtcatgata caacgcagtt tttcttatgc 10800 atgtttcata acaccacgaa catgtcgcag taagataatt tctgtaaatt catgattgcc 10860 ggtcataaac aagcccgtca ataattgtgg ctatatattc agtttataga gcaaaataat 10920 taagcacaat agcgcttaat ctcaaaatat gttatgttta tttttttcat attaaacata 10980 ctggttaaaa tcctctaaag gctgatcttc atctataaat caagatcata attacattta 11040 gacagtggtt tcatgtttat aaaaatgttc tttttgtgg aataaggaat atactaatca 11100 ataatcaacc atcgacccca ttacgatagt atgcaggcaa ccccccatta gagaggtacg 11160 tgtaatcagt ctctccagtt ttagtatttt tataagtcat tgttacataa acggctttta 11220 aacagtctcc tcgataataa gccatatctg gaaatttatt aaatactcga gtcattttac 11280 gcacggtcaa aaaagtaagt aatgtcgacg acttcttaca ttctatagaa acacctagaa 11340 tactcatttt cttttggaaa atatcctcag actctgattt gaacaatgca cgacctatag 11400 taaaccgtga ccaataagtt atattagtca atggtatatc caaaccatca ggtgtggata 11460 gtacgccgat agtccagtct ttggtatcga tagtgtagtt attgaactga gaagttaccg 11520 tatagtcttt ttggtcatct ctaaacaagg aaactaatac ctctacacta ttgaacgatt 11580 tatcttccgt aatgggtgga ataacgggaa tataaagtgg actagcgatg gatgaagtca 11640 cgaatataag acacgctatt aatccgtata tcatcatttt gatattactt ataataacga 11700 tttgtttaat ttttagttta tactattaat tgtaaatgat attattattt tttttaagta 11760 ttatcagctt tagtttatac tattactatt tgtaatattt agacatagat aaacgtgata 11820 aaagtctatt tgtttatatt tattgcggat agcagtattt ccctataaaa agtatacgtc 11880 ctgtgttgtc tttaatcatg tacatgaatg gatggtttat gtagaccttc gtacgatata 11940 ccatcgaaaa gttagtcata aatactcctg taacggccga tgcttctgta tactcctcat 12000 taacatctat aaacgtcgta tgtagaaatt tttctacagt gatagtttca ttacacatct 12060 tgctaaaatc tgcataatat ccgaatatat tagtaagtcc taaattttct aaaatcggta 12120 ccagattata cggttctgtc atttccactt taaactttgg catatacaag tctatacttt 12180 tagtagataa cataccacac cattttttaa atttttcatc tgttatattt ttttctatgt 12240 tatatatacc ttctatgtcg tccggtagta taattaccat actagagttt ccctcgtatg 12300 gaatatcgat aatagagaat cctccgaata attcattaat atgtacatat tgcaagttat 12360 tctcggtacc caccatcata tcaacgctgg taactatatt cttagaaata taaaacttgt 12420 ctgtatatgt aagatgttta gaaaatggat atttccacat tgctttaaaa tggacggcgc 12480 taacaactgt catacgagta ttaatggata gcggactagt caataaggaa ttaattttac 12540 catttgtcat cgtcttaacc cattcgttga ttagttcctt tgtttggtta gcattattaa 12600 agtttacagt ttgaaaatcg tcttttatt tttgtaggaa ggaggcgtgg aactcgatac 12660 tatcgctacc gtatatttta tttgcggtag ctagtgtcgc acaatacgga atatctacgt 12720 ccatgtcatt attgtcatcc ttcttatcat cgggtgtatt ctcattcata ttctctatat 12780 attttgatag ttgttcagct gtagaaccag ctgctccatg atttagaata gataaagtag 12840 ataaaataga aactggagaa atcaaaacat tttcatcagg gtgttttaag attagttctt 12900 taaagatatc catggtatag accaaacaat aacgataacg atatatatca taaataaata 12960 atgttaaatt tcagtttatg tttgtacccc gtattcatac ttaacaaatt ggtattgcgt 13020 acacaatcaa tcatattaca taccattaat aatgcaagca taaaaaatcg ttagtagatg 13080 tttctaaata taggttccgt aagcaaagaa tataagaatg aagcggtaat gataaaatca 13140 atcgttatct aaaatgatca tactcattta ttttattcta ttatattaac acatacattt 13200 ttaacagcaa cacattcaat attgtattgt tatttttata ttatttacac aattaacaat 13260 atattattag tttatattac tgaattaata atataaaatt cccaatcttg tcataaacac 13320 acactgagaa acagcataaa cacaaaatcc atcaaaaatg ttgataaatt atctgatgtt 13380 gttgttcgct gctatgataa tcagatcatt cgccgatagt ggtaacgcta tcgaaacgac 13440 atcgccagaa attacaaacg ctacaacaga tattccagct atcagattat gcggtccaga 13500 gggagatgga tattgtttac acggtgactg tatccacgct agagatatcg acggtatgta 13560 ttgtagatgc tctcatggtt atacaggcat tagatgtcag catgtagtat tagtagacta 13620 tcaacgttca gaaaacccaa acactacaac gtcatatatc ccatctcccg gtattatgct 13680 tgtatagta ggcattatta ttattacgtg ttgtctatta tctgtttata ggttcactcg 13740 acgaactaaa ctacttatac aagatatggt tgtgccataa tttttataaa ttttttttat 13800 gagtattttt acaaaaatgt ataaagtgta tgtcttatgt atatttataa aaatgctaag 13860 tatgcgatgt atctatgtta tttgtattta tctaaacaat acctctacct ctagatatta 13920 tacaaaaatt ttttattcg gcatattaaa gtaaaatcta gttaccttga aaatgaatac 13980 agtgggtggt tccgtatcac cagtaagaac ataatagtca aatacagtat ccgattgaga 14040 ttttgcatac aatactagtc tagaaagaaa tttgtaatca tcttctgtga cgggagtcca 14100 tatatctgta tcatcgtcta gtttatcagt gtcccatgct atatttctgt tatcatcatt 14160 agttaatgaa aataactctc gcgcttcaga aaagtcaaat attgtatcca tacatacatc 14220 tccaaaacta tcgctttatac gtttatcttt aacgatacct atacctagat ggttatttac 14280 taacagacat tttccagatc tattgactat aactcctata gtttccacat caaccaagta 14340 atgatcatct attgttatat aacaataaca taactctttt ccatttttat cagtatgtat 14400 atctatatca acgtcgtcgt tgtagtgaat agtagtcatt gatctattat atgaaacgga 14460 tatgtctaga acggcaattg ttttacgtcc agttaacact ttctttgatt taaagtctag 14520 agtctttgca aacataatat ccttatccga ctttatattt cctgtagggt ggtataattt 14580 tattttgcct ccacatatcg gtgtttccaa atatattact agacaatatt ccatatagtt 14640 attagttaag ggtacccaat tagaacacgt acgcttatta tcatcatttg gatcgtattt 14700 cataaaagtt attgtgttat cgatgtcaac acattctaca ttttttaatc gtctatatag 14760 tatttttctg atattttcta taatatcaga attgtcttcc atcggaagtt gtatactatc 14820 ggaatcagtt acatgtttaa ataattctct gatgtcattc ctttatacaat caaattcatt 14880 attaaacagt ttaatagtct gtagaccttt atcgtcgtaa atatccattg tctttattagt 14940 tacgcttatt tttatgtgtt ttacgttgct ttattatatt ttataagaat gattgtttga 15000 cgaatcacga gaactattaa gacacattat taggtatata ttataaaaaa gtttttgatt 15060 acgatgttat aagaggaaag aggacacatt aacatcatac atcaattaac tacattctta 15120 taacatcgta atcaaaagaa ttgcaatttt gatgtataac aactgtcaat gggttatgga 15180 attgtatatt acatattata cggtatgttg gtaacgacaa ataccggtcg gtaattgtct 15240 gccggtgtaa tagaattata tatatctatc tattacaccg gccttgtata cataataata 15300 agttgtggta gtatgatctc catatttata atttaggact ttgtattcag tatttttgga 15360 atcataaaaa ataaaaaaaa gttttaactaa tttaaaattt aaaaagtatt tacatttttt 15420 tcactgttta gtcgcggata tggaattcga tcctgccaaa atcaatacat catctataga 15480 tcatgtaaca atattacaat acatagatga accaaatgat ataagactaa cagtatgcat 15540 tatccgaaat attatatcaa tatcacaaaa ataaatccac atttggctaa tcaatttcgg 15600 gcttggaaaa aacgtatcgc cggaagggac tatataacta acttatctag agatacagga 15660 atacaacaat caaaacttac tgaaactata cgtaactgtc aaaaaaatag aaacatatat 15720 ggtctatata tacactacaa tttagttat aatgtggtta ttgattggat aaccgatgtg 15780 attatcaatc aatattaaga gggttggtaa attggtacat agctaataat acctatactc 15840 caaatacacc caataataca acaaccattt ctgagttgga tatcatcaaa atactggata 15900 aatacgagga cgtgtataga gtaagtaaag aaaaagaatg tggaatttgc tatgaagttg 15960 tttactcaaa acgatagata ctttggttta ttggattcgt gtaatcatat attttgcata 16020 acatgtatca atatatggca tagaacacga agagaaaccg gtgcgtcgga taattgtcct 16080 atatgccgta cccgttttag aaacataaca atgagcaagt tttataagct agttaactaa 16140 taaataaaaa gtttaatttg ttgacgacgt atgtcgttat tttttctcgt ataaaagatt 16200 aatttgattc taatataatc tttagtattg gataaatatc aattcaaatt aattccatta 16260 gattatatca taaataaaaa tagtagcacg cactacttca gccaaatatt cttttttgaa 16320 acgccatcta tcgtagtgag gacacaagtg aacctataat tatcaaattt attagtatca 16380 gtcacatgaa ggactttctg tagagtgacg attccactat ctgtggtacg aacggtttca 16440 tcttctttga tgccatcacc cagatgttct ataaacttgg tatcctcgtc cgatttcata 16500 tcctttgcca accaatacat atagctaaac tcaggcatat gttccacaca tcctgaacaa 16560 tgaaattctc cagaagatgt tacaatgtct agatttggac atttggtttc aaccgcgtta 16620 acatatgagt gaacacaccc atacatgaaa gcgatgagaa ataggattct catcttgcca 16680 aaatatcact agaaaaatt tatttatcaa ttttaaaggt ataaaaaata cctattgttg 16740 ctcgaatatt ttgtatttga tggtatacgg aagattagaa atgtaggtat tatcatcaac 16800 tgattctatg gttttatgta ttctatcatg tttcactatt gcgttggaaa taatatcata 16860 tgcttccaca tatattttat tttgttttaa ctcataatac tcacgtaatt ctggattatt 16920 ggcatatcta tgaataattt tagctccatg atcagtaaat attaatgaga acatagtatt 16980 accacctacc attatttttt tcatctcatt caattcttaa ttgcaaagat ctatataatc 17040 attatagcgt tgacttatgg actctgaaat cttagacgat gtacagtcat ctataatcat 17100 ggcatattta atacattgtt ttatagcata gtagttatct acgatgttag atatttttct 17160 caataaatca atcacataat ctaatgtagg tttatgacat aatagcattt tcagcagttc 17220 aatgttttta gattcgttga tggcaatggc tatacatgta tatccgttat ttgatctaat 17280 gttgacatct gaaccggatt ctagcagtaa agatactaga gattgtttat tatatctaac 17340 agccttgtga agaagtgttt ctcctcgttt gtcaatcatg ttaatgtctt taagataagg 17400 taggcaaatg tttatagtac taagaattgg gcaagcataa gacatgtcac aaagaccctt 17460 tttgtatgta taagtgtaaa aattataaca tccatagttg gatttacata ggtgtccaat 17520 cgggatctct ccatcatcga gataattgat ggcatctccc ttcctttttt agtagatatt 17580 tcatcgtgta agaatcaata ttaatatttc taaagtatcc gtgtatagcc tctttattta 17640 ccacagttcc atattccact agaggtat cgccgaatgt catatactca attagtatat 17700 gttggaggac atccgagttc attgttttca atatcaaaga gatggtttcc ttatcatttc 17760 tccatagtgg tacaatacta cacattattc cgtgcggctt tccattctcc aaaaacaatt 17820 tgaccaaatc tacatcttta ttgtatctat aatcactatt tagataatca gccataatta 17880 ctcgagtgca acatgttaga tcgtctatat atgaataagc cgtgttatct attcctttca 17940 ttaacaattt aacgatgtct atatctatat gagatgactt aatataatat tgaagagctg 18000 tacaatagtt tttatctata aaagacggct tgattccgtg attaattaga catttaacaa 18060 cttccggacg cacatatgct ctcgtatccg actttgaata cagatgagag atgatataca 18120 gatgcaatac ggtaccgcaa tttcgtagtt gataatcatc atacgcgtat cagtactcgt 18180 cctcataaag aacactgcag ccatttttta tgaacaaatc aataatttta ggaacaggat 18240 cattgtcatt acataatttt ctataactga acgatggttt tcacatttaa cactcaagtc 18300 aaatccatgt tctaccaaca cctttatcaa gtcaacgtct acatttttgg atttcatata 18360 gctgaatata ttaaagtcat ttatgttgct aaatccagtg gcttctagta gagccatcgc 18420 tatatccttt aactttaaca tgtctactat ttgtgtattc ttctaatggg gtaagctgtc 18480 tccaattttt gcgtaatgga ttagtgccac tgtctagtag tagtttgacg acctcgacat 18540 tattacaatg ctcattaaaa aggtatgcgt gtaaagcatt attcttgaat tggttcctgg 18600 tatcattagg atctctgtct ttcaacatct gtttaagttc atcaagagcc acctcctcat 18660 tttccaaata gtcaaacatt ttgactgaat gagctactgt gaactctata cacccacaca 18720 actaatgtca ttaaatatca tgtcaaaaac ttgtacaatt attaataaaa ataatttagt 18780 gtttaaattt taccagttcc agattttaca cctccgttaa ccccactttt tacaccactg 18840 gacgatcctc ctccccacat tccaccgcca ccagatgtat aagttttaga tcctttatta 18900 ctaccatcat gtccatggat aaagacactc cacatgccgc cactaccccc tttagaagac 18960 atattaataa gacttaagga caagtttaac aataaaatta atcacgagta ccctactacc 19020 aacctacact attatatgat tatagtttct atttttacag taccttgact aaagtttcta 19080 gtcacaagag caatactacc aacctacact attatatgat tatagtttct atttttatag 19140 gaacgcgtac gagaaaatca aatgtctaat ttctaacggt agtgttgata aacgattatc 19200 gtcaatggat acctcctcta tcatgtcgtc tattttctta ctttgttcta ttaacttatt 19260 agcattatat attatttgat tataaaactt atattgctta ttagcccaat ctgtaaatat 19320 cggattatta acatatcgtt tctttgtagg tttatttaac atgtacatca ctgtaagcat 19380 gtccgtacca tttattttaa tttgacgcat atccgcaatt tctttttcgc agtcggttat 19440 aaattctata tatgatggat acatgctaca tgtgtactta taatcgacta atatgaagta 19500 cttgatacat attttcagta acgatttatt attaccacct atgaataagt acctgtgatc 19560 gtctaggtaa tcaactgttt tcttaataca ttcgatggtt ggtaatttac tcagaataat 19620 ttccaatatc ttaatatata attctgctat ttctgggata tatttatctg ccagtataac 19680 acaaatagta atacatgtaa acccatattt tgttattata ttaatgtctg cgccattatc 19740 tattaaccat tctactaggc tgacactatg cgacttaata caatgataaa gtatactaca 19800 tccatgttta tctattttgt ttatatcatt aatatacggc ttacaaagtt ttagtatcga 19860 taacacatcc aactcacgca tagagaaggt agggaataat ggcataatat ttattaggtt 19920 atcatcattg tcattatcta caactaagtt tccatttttt aaaatatact cgacaacttt 19980 aggatctcta ttgccaaatt tttgaaaata tttatttata tgcttaaatc tatataatgt 20040 agctccttca tcaatcatac atttaataac attgatgtat actgtatgat aagatacata 20100 ttctaacaat agatcttgta tagaatctgt atatctttta agaattgtgg atattaggat 20160 attattacgt aaactattac acaattctaa aatataaaac gtatcacggt cgaataatag 20220 ttgatcaact atataattat cgattttgtg atttttcttc ctaaactgtt tacgtaaata 20280 gttataga atattcatta gttcatgacc actatagtta ctatcgaata acgcgtcaaa 20340 tatttcccgt ttaatatcgc atttgtcaag ataataatag agtgtggtat gttcacgata 20400 agtataataa cgcatctctt tttcgtgtga aattaaatag tttattacgt ccaaagatgt 20460 agcataacca tcttgtgacc tagtaataat ataataatag agaactgttt tacccattct 20520 atcatcataa tcagtggtgt agtcgtaatc gtaatcgtct aattcatcat cccaattata 20580 atattcacca gcacgtctaa tctgttctat tttgatcttg tatccatact gtatgttgct 20640 acatgtaggt attcctttat ccaataatag tttaaacaca tctacattgg gatttgatgt 20700 tgtagcgtat ttttctacaa tattaatacc atttttgata ctatttattt ctataccttt 20760 cgaaattagt aatttcaata agtctatatc gatgttatca gaacatagat attcgaatat 20820 atcaaaatca ttgatatttt tatagtcgac tgacgacaat aacaaaatca caacatcgtt 20880 tttgatatta ttatttttct tggtaacgta tgcctttaat ggagtttcac catcatactc 20940 atataatgga tttgcaccac tttctatcaa tgattgtgca ctgctggcat cgatgttaaa 21000 tgttttacaa ctatcataga gtatcttatc gttaaccatg attggttgtt gatgctatcg 21060 catttttttg gtttctttca tttcagttat gtatggattt agcacgtttg ggaagcatga 21120 gctcatatga tttcagtact gtagtgtcag tactattagt ttcgatcaga tcaatgtcta 21180 aatctataga atcaaaacac gatagtcag aagataatga atatctgtac gcttcttgtt 21240 gtactgtaac ttctggtttt gttagatggt tgcatcgtgc tttaacatca atggtacaaa 21300 ttttatcctc gctttgtgta tcatattcgt ccctactata aaattgtata ttcagattat 21360 catgagatgt gtatacgcta acggtatcaa taaacggagc acaccattta gtcataaccg 21420 taatccaaaa atttttaaag tatatcttaa cgaaagaagt tgtgtcattg tctacagtgt 21480 atggtattag atcctcataa gtgtatatat ctagagtaat gtttaattta tcaaatggtt 21540 gataatatgg atcgtcgtgg caatttccta agacgaaaat aagacataaa cacgcaataa 21600 atctaatcga agacatggtt actccttaaa aaaatacgaa taatcacctt ggctatttag 21660 taagtgtcat ttaacactat actcatatta atccatggac tcataatctc tatacgggat 21720 taacggatgt tctatatacg gggatgagta gttctcttct ttaactttat actttttaact 21780 aatcatattt agactgatgt atgggtaata gtgtttgaag agctcgttct catcatcaga 21840 ataaatcaat atctctgttt ttttgttata cagatgtatt acagcctcat atattacgta 21900 atagaacgtg tcatctacct tattaacttt caccgcatag ttgtttgcaa atacggttaa 21960 tcctttgacc tcgtcgattt ccgaccaatc tgggcgtata atgaatctaa actttaattt 22020 cttgtaatca ttcgaaataa tttttagttt gcatccgtag ttatcccctt tatgtaactg 22080 taaatttctc aacgcgatat ctccattaat aatgatgtcg aattcgtgct gtatacccat 22140 actgaatgga tgaacgaata ccgacggcgt taatagtaat ttactttttc atctttacat 22200 attgggtact agtttacta tcataagttt ataaattcca caagctacta tggaataagc 22260 caaccatctt agtataacac acatgtctta aagtttatta attaattaca tgttgtttta 22320 tatatcgcta cgaatttaaa cagagaaatc agtttaggaa aaaaaattat ctatctacat 22380 catcacgtct ctgtattcta cgatagagtg ctactttaag atgagacata tccgtgtcat 22440 caaaaatata ctccattaaa atgattattc cggcagcgaa cttgatattg gatatatcac 22500 aacctttgtt aatatctacg acaatagaca gcagtcccat ggttccataa acagtgagtt 22560 tatctttctt tgaagagata ttttgtagag atcttataaa actgtcgaat gacatcgcat 22620 ttatatcttt agctaaatcg tatatgttac catcgtaata tctaaccgcg tctatcttaa 22680 acgtttccat cgctttaaag acgtttccga tagatggtct catttcatca gtcatactga 22740 gccaacaat ataatcgtgt ataacatctt tgatagaatc agactctaaa gaaaacgaat 22800 cggctttatt atacgcattc atgataaact taatgaaaaa tgtttttcgt tgtttaagtt 22860 ggatgaatag tatgtcttaa taattgttat tatttcatta attaatattt agtaacgagt 22920 acactctata aaaacgagaa tgacataact agttatcaaa gtgtctagga cgcgtaattt 22980 tcatatggta tagatcctgt aagcattgtc tgtattctgg agctattttc tctatcgcat 23040 tagtgagttc agaatatgtt ataaatttaa atcgaataac gaacataact ttagtaaagt 23100 cgtctatatt aactctttta ttttctagcc atcgtaatac catgtttaag atagtatatt 23160 ctctagttac tacgatctca tcgttgtcta gaatatcaca tactgaatct acatccaatt 23220 ttagaaattg gtctgtgtta catatctctt ctatattatt gttgatgtat tgtcgtagaa 23280 aactattacg tagaccattt tctttataaa acgaatatat agtactccaa ttatctttac 23340 cgatatattt gcacacataa tccattctct caatcactac atctttaaga ttttcgttgt 23400 taagatattt ggctaaacta tataattcta ttagatcatc aacagaatca gtatatattt 23460 ttctagatcc aaagacgaac tctttggcgt cctctataat attcccagaa aagatatttt 23520 cgtgttttag tttatcgaga tctgatctgt tcatatacgc catgattgta cggtacgtta 23580 tgataaccgc ataaaataaa aatccatttt catttttaac caatactatt cataattgag 23640 attgatgtaa tactttgtta ctttgaacgt aaagacagta cacggatccg tatctccaac 23700 aagcacgtag taatcaaatt tggtgttgtt aaacttcgca atattcatca atttagatag 23760 aaacttatac tcatcatctg ttttaggaat ccatgtatta ttaccacttt ccaacttatc 23820 attatcccag gctatgtttc gtccatcatc gttgcgcaga gtgaataatt cttttgtatt 23880 cggtagttca aatatatgat ccatgcatag atcggtaaag ctattgtaga tgtgattttt 23940 cctaaatcta atataaaact cgtttactag caaacacttt cctgatttat cgaccaagac 24000 acatatggtt tctaaatcta tcaagtggtg gggatccata gttatgacgc agtaacatag 24060 attattacat tcttgactgt cgctaatatc taaatattta ttgttatcgt attggattct 24120 gcatatagat ggcttgtatg tcaaagatat agaacacata accaatttat agtcgcgctt 24180 tacattctcg aatctaaagt taagagattt agaaaacatt atatcctcgg atgatgttat 24240 cactgtttct ggagtaggat atattaaagt ctttacagat ttcgtccgat tcaaataaat 24300 cactaaataa tatcccacat tatcatctgt tagagtagta tcattaaatc tattatattt 24360 tatgaaagat atatcactgc tcacctctat atttcgtaca tttttaaact gtttgtataa 24420 tatctctctg atacaatcag atatatctat tgtgtcggta gacgataccg ttacatttga 24480 attaatggtg ttccatttta caacttttaa caagttgacc aattcatttc taatagtatc 24540 aaactctcca tgattaaata ttttaatagt atccatttta tatcactacg gacacaaagt 24600 agctgacata aaccattgta taatttttat gttttatgtt tattagcgta cacattttgg 24660 aagttccggc ttccatgtat ttcctggaga gcaagtagat gatgaggaac cagatagttt 24720 atatccgtac ttgcacttaa agtctacatt gtcgttgtat gagtatgatc ttttaaaccc 24780 gctagacaag tatccgtttg atattgtagg atgtggacat ttaacaatct gacacgtggg 24840 tggatcggac cattctcctc ctgaacacag gacaccagag ttaccaatca acgaatatcc 24900 actattgcaa ctataagtta caacgctccc atcggtataa aaatcctcgt atccgttatg 24960 tcttccgttg gatatagatg gaggggattg gcatttaaca gattcacaaa taggtgcctc 25020 gggattccat accatagatc cagtagatcc taattcacaa tacgatttag attcaccgat 25080 caaatgatat ccgctattac aagagtacgt tatactagag ccaaagtcta ctccaccaat 25140 atcaagttgg ccattatcga tatctcgagg cgatgggcat ctccgtttaa tacattgatt 25200 aaagagtgtc catccagtac ctgtacattt agcatatata ggtcccattt tttgctttct 25260 gtatccaggt agacatagat attctatagt gtctcctatg ttgtaattag cattagcatc 25320 agtctccaca ctattcttaa atttcatatt aatgggtcgt gacggaatag tacagcatga 25380 tagaacgcat cctattccca acaatgtcag gaacgtcacg ctctccacct tcatatttat 25440 ttatccgtaa aaatgttatc ctggacatcg tacaaataat aaaaagccca tatatgttcg 25500 ctattgtaga aattgttttt cacagttgct caaaaacgat ggcagtgact tatgagttac 25560 gttacacttt ggagtctcat ctttagtaaa catatcataa tattcgatat tacgagttga 25620 catatcgaac aaattccaag tatttgattt tggataatat tcgtattttg catctgctat 25680 aattaagata taatcaccgc aagaacacac gaacatcttt cctacatggt taaagtacat 25740 gtataattct atccatttgt cttccttaac tatatatttg tatagataat tacgagtctc 25800 gtgagtaatt ccagtaatta catagatgtc gccgtcgtac tctacagcat aaactatact 25860 atgatgtcta ggcatggggag acttttttat ccaacgattt ttagtgaaac attccacatc 25920 gtttaatact acatattttt catacgtggt ataaactcca cccattacat atatatcatc 25980 gtttacgaat accgacgcgc ctgaatatct aggagtaatt aagtttggaa gtcttatcca 26040 tttcgaagtg ccgtgtttca aatattctgc cacacccgtt gaaatagaaa attctaatcc 26100 tcctattaca tataactttc catcgttaac acaagtacta acttctgatt ttaacgacga 26160 catattagta accgttttcc attttttcgt ttcaagatct acccgcgata cggaataaac 26220 atgtctattg ttaatcatgc cgccaataat gtatagacaa ttatgtaaaa catttgcatt 26280 atagaattgt ctatctgtat taccgactat cgtccaatat tctgttctag gagagtaatg 26340 ggttatgtg gatatataat cagagttttt aatgactact atattatgtt ttataccatt 26400 tcgtgtcact ggctttgtag atttggatat agttaatccc aacaatgata tagcattgcg 26460 catagtatta gtcataaact tgggatgtaa aatgttgatg atatctacat cgtttggatt 26520 tttatgtatc cactttaata atatcatagc tgtaacatcc tcatgattta cgttaacgtt 26580 ttcgtgggat aagatagttg tcagttcatc ctttgataat tttccaaatt ctggatcgga 26640 tgtcaccgca gtaatattgt tgattatttc tgacatcgac gcattatata gttttttaat 26700 tccatatctt ttagaaaagt taaacatcct tatacaattt gtggaattaa tattatgaat 26760 catagttttt acacatagat ctactacagg cggaacatca attattatgg cagcaactag 26820 tatcatttct acattgttta tggtgatgtt tatcttcttc cagcgtatat agtctaatag 26880 cgattcaaac gcgtgatagt ttataccatt caatataatc gcttcatcct ttagatggtg 26940 atcctgaatt cgtttaaaaa aattatacgg agatgccgta ataatttcct tattcacttg 27000 tataatttcc ccattgatag aaaatatcac gctttccatt cttgaagtac tataagtaat 27060 tatagtataa tgtaaaggtt tatatattca atatttttta taaaaaaatc attttgacat 27120 taattccttt ttaaatttcc gtctatcatc tatagaaacg tattctatga atttataaaa 27180 tgcttttacg tgtcctatcg taggcgatag aaccgctaaa aagcctatcg aatttctaca 27240 aaagaatctg ttatatggta tagggagagt ataaaacatt aaatgtccgt acttattaaa 27300 gtattcagta gccaatccta actctttcga atacttatta atggctcttg ttctgtacga 27360 atctattttt ttgaacaacg gacctagtgg tatatcttgt tctatgtatc taaaataatg 27420 tctgactaga tccgttagtt taatatcctc agtcatcttg tctagaatgg caaatctaac 27480 tgcgggttta ggctttagtt tagtttttat atctacatct atgtctttat ctaacaccaa 27540 aaatataata gctaatattt tattacaatc atccggatat tcttctacga tctcactaac 27600 taatgtttct ttggttatac tagtatagtc actatcggac aaataaagaa aatcagatga 27660 tcgatgaata atacatttaa attcatcatc tgtaagattt ttgagatgtc ttattaaaat 27720 attattaggg tcagtactca ttatcattag gcagctatta cttattttat tatttttcac 27780 catatagatc aatcattaga tcatcaaaat atgtttcaat catcctaaag agtatggtga 27840 atgactcttc ccatctaatt tctgaacgtt caccaatgtc tctagccact ttggcactaa 27900 tagcgatcat tcgcttagcg tcttctatat tattaactgg ttgattcaat ctatctagca 27960 atggaccgtc ggacagcgtc attctcatgt tcttaatcaa tgtacataca tcgccgtcat 28020 ctaccaattc atccaacaac ataagctttt taaaatcatc attataatag gtttgatcgt 28080 tgtcatttct ccaaagaata tatctaataa gtagagtcct catgcttagt aatttaacta 28140 ttttagttaa caactatttt ttatgttaaa tcaattagta caccgctatg tttaatactt 28200 attcatattt tagtttttag gattgagaat caatacaaaa aattaatgca tcattaattt 28260 tagaaatact tagtttccac gtagttaatg aaacatttga actcatcgta caggacgttc 28320 tcgtacagga cgtaactata aaccggttta tatttgttca agatagatac aaatccgata 28380 acttttttta cgaattctac gggatccact ttaaaagtgt cataccgggt tctttttatt 28440 cttttaaaca gatcaatggt gtgatgttga ttaggtcttt tacgaatttg atatagaata 28500 gcgttcacat atcctccata atggtcaatc gccatttgtt cgtatgtcat aaattcttta 28560 attatatgac actgtgtatt atttagttca tccttgttca tcattaggaa tctatccaaa 28620 atggcaatta tactagaact ataggtgcgt tgtatacaca tattgatgtg tctgtttata 28680 caatccatga tatttggatc catgctacta ccttcgggta aaattgtagc atcatatacc 28740 atttctagta ctttaggttc attattatcc attgcagagg acgtcatgat cgaatcctaa 28800 aaaaatatat tatttttatg ttattttgtt aaaaataatc atcgaatact tcgtaagata 28860 ctccttcatg aacataatca gttacaaaac gtttatatga agtaaagtat ctacgatttt 28920 tacaaaagtc cggatgcata agtacaaagt acgcgataaa cggaataata atagatttat 28980 ctagtctatc tttttctata gctttcatag ttagatacat ggtctcagaa gtaggattat 29040 gtaacatcag cttcgataaa atgactgggt tatttagtct tacacattcg ctcatacatg 29100 tatgaccgtt aactacaaag tctacactaa aatgattgaa caatagatag tctaccattg 29160 tttcgtattc agatagtaca gcgtagtaca tagcatcttc acaaattata tcattgtcta 29220 atagatattt gacgcatctt atggatccca cttcaacagc catcttaaaa tcggtagaat 29280 catattgctt tcctttatca ttaataattt ctaaaacatc atctctatca taaaagatac 29340 aaatattaac tgtttgatcc gtaataacat tgctagtcga tagcaatttg ttaataagat 29400 gcgctgggct caatgtctta ataagaagtg taagaggact atctccgaat ttgttttgtt 29460 tattaacatc cgttgatgga agtaaaagat ctataatgtc tacattcttg actgttttag 29520 agcatacaat atggagaggt gtatttccat catgatctgg ttttgaggga ctaattccta 29580 gtttcatcat ccatgagatt gtagaagctt ttggattgtc tgacataaga tgtctatgaa 29640 tatgattttt gccaaattta tccactatcc tggcttcgaa tccgatggac attatttttt 29700 taaacactct ttctgaagga tctgtacacg ccaacaacgg accacatcct tcttcatcaa 29760 ccgagttgtt aatcttggct ccatactgta ccaataaatt tattctctct atgacttcat 29820 catctgttcc cgagagataa tatagaggtg ttttattatg tttatcacac gcgtttggat 29880 ctgcgccgtg cgtcagcagc atcgcgacta ttctattatt attaatttta gaagctatat 29940 gcaatggata atttccatca tcatccgtct catttggaga gtatcctcta tgaagaagtt 30000 cttcgacaaa tcgttcatct agtcctttaa ttccacaata cgcatgtaga atgtgataat 30060 tatttccaga aggttcgata gcttgtagca tattcctaaa tacatctaaa tttttactat 30120 tatatttggc ataaagagat agataatact cggccgacat aatgttgtcc attgtagtat 30180 aaaaattaat atttctattt ctatttctgt atatttgcaa caatttactc tctataacaa 30240 atatcataac ttagttcttt tatgtcaaga aggcactggt ttagttcatc tataaatgtc 30300 acgccataac taccacgcat gctatactca gaattatgat aaagatattt atccttgggg 30360 tgtaggtaat ggggattaat ctttgttgga tcagtctcta agttaacaca tgtcacacat 30420 gatccattta tagttatatc acacgatgat gatttatgaa ttgattccgg aagatcgcta 30480 tcgtattttg tggttccaca attcatttcc atacatgtta ttgtcacact aatattatga 30540 tgaactttat ctagccgctg agtggtaaac aacagaacag atagtttat atctttacca 30600 acaccctcag ccgctgccac aaatctctga tccgtatcca tgatggtcat gtttatttct 30660 agtccgtatc cagtcaacac tatgttagca tttctgtcga tatagctttc actcatatga 30720 cactcaccaa taatagtaga attaatgtcg taatttacac caatagtgag ttcggcggca 30780 aagtaccaat accggtaatc ttgtcgagga ggacatatag tattcttgta ttctaccgaa 30840 tacccgagag atgcgataca aaagagtaag actaatttgt aaaccatctt actcaaaata 30900 tgtaacaata gtacgatgca atgagtaaga caataggaaa tctatcttat atacacataa 30960 ttattctatc aattttacca attagttagt gtaatgttaa caaaaatgtg ggagaatcta 31020 attagttttt ctttacacaa ttgacgtaca tgagtttgag ttccttgttt ttgctaatta 31080 tttcatccaa tttattattc ttgacgatat cgagatcttt tgtataggag tcagacttgt 31140 attcaacatg cttttctata atcattttag ctatttcggc atcatccaat agtacatttt 31200 ccagattagc agaatagata ttaatgtcgt atttgaacag agcctgtaac atctcaatgt 31260 ctttattatc tatagccaat ttaatgtccg gaatgaagag aagggaatta ttggtgtttg 31320 tcgacgtcat atagtcgagc aagagaatca tcatatccac gtgtccattt tttatagtga 31380 tgtgaataca actaaggaga atagccagat caaaagtaga tggtatctct gaaagaaagt 31440 aggaaacaat acttacatca ttaagcatga cggcatgata aaatgaagtt ttccatccag 31500 ttttcccata gaacatcagt ctccaatttt tcttaacaaa cagttttacc gtttgcatgt 31560 taccactatc aaccgcataa tacaatgcag tgtttccctt gtcatcaaat tgtgaatcat 31620 ccagtccact gaatagcaaa atcttacta ttttagtatc ttccaatgtg gctgcctgat 31680 gtaatggaaa ttcattctct agaagatttt tcaatgctcc agcgttcaac aacgtacata 31740 ctagacgcac gttattatca gctattgcat aatacaaggc actatgaccg ttgatatccg 31800 ccttaaatgc atctttgcta gagagaaagc ttttcagctg cttagacttc caagtattaa 31860 ttcgtgacag atccatgtct gaaacgagac gctaattagt gtatattttt tcatttttta 31920 taattttgtc atattgcacc agaattaata atatctctaa tagatctgat tagtagatac 31980 atggctatcg caaaacaaca tatacacatt taataaaaat aatatttatt aagaaaattc 32040 agatttcacg tacccatcaa tataaataaa ataatgattc cttacaccgt acccatatta 32100 aggagattcc accttaccca taaacaatat aaatccagta atatcatgtc tgatgatgaa 32160 cacaaatggt gtattaaatt ccagtttttc aggagatgat ctcgccgtag ctaccataat 32220 agtagatgcc tctgctacag ttccttgttc gtcgacatct atctttgcat tctgaaacat 32280 tttataaata tataatgggt ccctagtcat atgtttaaac gacgcattat ctggattaaa 32340 catactagga gccatcattt cggctatcga cttaatatcc ctcttatttt cgatagaaaa 32400 tttagggagt ttaagattgt acactttatt ccctaattga aacgaccaat agtctaattt 32460 tgcagccgta atagaatctg tgaaatgggt catattatca cctattgcca ggtacatact 32520 aatattagca tccttatacg gaaggcgtac catgtcatat tctttgtcat cgattgtgat 32580 tgtatttcct tgcaatttag taactacgtt catcatggga accgttttcg taccgtactt 32640 attagtaaaa ctagcattgc gtgttttagt gatatcaaac ggatattgcc atataccttt 32700 aaaatatata gtattaatga ttgcccatag agtattattg tcgagcatat tagaatctac 32760 tacattagac ataccggatc tacgttctac tatagaatta attttattaa ccgcatctcg 32820 tctaaagttt aatctatata ggccgaatct atgatattgt tgataataca acggtttaat 32880 acacacagta ttatctacga aactttgata agttagatca gtgtacgtat atttagatgt 32940 tttcagctta gctaatcctg atattaattc tgtaaatgct ggacccagat ctctttttct 33000 caaatccata gtcttcaata attctattct agtattacct gatgcaggca atagcgacat 33060 aaacatagaa aacgaataac caaacggcga gaagacaata ttatcatctt gaatattttt 33120 atacgctact ataccggcat tggtaaatcc ttgcagacga taggtagacg ctgaacacgc 33180 taacgatagt atcaataacg caatcatgat tttatggtat taataattaa ccctatttttt 33240 atgttcggta taaaaaatt attgatgtct acacatcctt ttgtaattga catctatata 33300 tccttttgta taatcaactc taatcacttt aacttttaca gttttcccta ccagtttatc 33360 cctatattca acatatctat ccatatgcat cttaacactc tctgccaaga tagcttcaga 33420 gtgaggatag tcaaaaagat aaatatatag agcataatca ttctcgtata ctctgccctt 33480 tattacatca cccgcattgg gcaacgaata acaaaatgca agcatcttgt taacgggctc 33540 gtaaattggg ataaaaatta tgtttttata tctattttat tcaagagaat attcaggaat 33600 ttctttttcc ggttgtatct catcgcagta tatatcattt gtacattgtt tcatattttt 33660 taatagttta caccttttag taggactagt atcgtacaat tcatagctgt attttgaatt 33720 ccaatcacgc ataaaaatat cttccaattg ttgacgaaga cctaatccat catccggtgt 33780 aatattaata gatgctccac atgtatccgt aaagtaattt cctgtccaat ttgaggtacc 33840 tatataggcc gttttatcgg ttaccatata tttggcatgg tttaccctag aatacggaat 33900 gggaggatca gcatctggta caataaatag ctttacttct atatttatgt ttttagattt 33960 tagcatagcg atagatctta aaaagtttct catgataaac gaagatcgtt gccagcaact 34020 aatcaatagc ttaacggata cttgtctgtc tatagcggat cttcttaatt catcttctat 34080 ataaggccaa aacaaaattt tacccgcctt cgaataaata atagggataa agttcataac 34140 agatacataa acgaatttac tcgcatttct aatacatgac aataaagcgg ttaaatcatt 34200 ggttctttcc atagtacata gttgttgcgg cgcagaagca ataaatacag agtgtggaac 34260 accacttacg ttaatactaa gaggatgatc tgtattataa tacgacggat aaaagttttt 34320 ccaattatat ggtagattgt taactccaag ataccagtat acctcaaaaa tttgagtgag 34380 atccgctgcc aagttcctat tattgaagat cgcaataccc aattccttga cctgagttag 34440 tgatctccaa tccatgttag cgcttcctaa ataaatatgt gtattatcag atatccaaaa 34500 ttttgtatga agaactcctc ctaggatatt tgtaatatct atgtatcgta cttcaactcc 34560 ggccatttgt agtctttcaa catcctttaa tggtttgtta gatttattga cggctactct 34620 aactcgtact cctcttttgg gtaattgtac aatctcgttt aatattatcg tgccgaaatt 34680 cgtacccact tcatccgata aactccaata aaaagatgat atatctagtg tttttgtggt 34740 attggataga atttccctcc acatgttaaa tgtagacaaa tatactttat caaattgcat 34800 acctatagga atagtctctg taatcactgc gattgtatta tccggattca ttttatttgt 34860 taaaaaataa tcctatatca cttcactcta ttaaaaatcc aagtttctat ttctttcatg 34920 actgattttt taacttcatc cgtttcctta tgaagatgat gtttggcacc ttcataaatt 34980 tttattctc tattacaatt tgcatgttgc atgaaataat atgcacctaa aacatcgcta 35040 atcttattgt ttgttccctg gagtatgaga gtcggggggt gttaatcttg gaaattattt 35100 ttctaacctt gttggtagcc ttcaagacct gactagcaaa tccagcctta attttttcat 35160 gattgactaa tgggtcgtat tggtatttat aaactttatc catatctcta gatactgatt 35220 ctggacatag ctttccgact ggcgcatttg gtgtgatggt tcccataagt ttggcagcta 35280 gcagattcag ttttgaaaca gcatctgcat taactagagg agacattaga atcattgctg 35340 taaacaagtt tggattatcg taagaggcta gctcccatgg aatgacccaa taagtagatt 35400 taatagttac cacgtgctgt accaaagtca tcaatcatca ttttttcacc attacttctt 35460 ccatgtccaa tatgatcatg tgagaatact aaaattccta acgatgatat gttttcagct 35520 agttcgtcat aacgtccaga atgtttacca gctccatgac ttatgaatac taatgcctta 35580 ggatatgtaa taggtttcca atatatgtaa tcattgtcca gattgaacat acagtttgca 35640 ctcatgattc acgttatata actatcaata ttaacagttc gtttgatgat catattattt 35700 ttatgtttta ttgataattg taaaacata caattaaatc aatatagagg aaggagacgg 35760 ctactgtctt ttgtgagata gtcatggcga ctaaattaga ttatgaggat gctgtttttt 35820 actttgtgga tgatgataaa atatgtagtc gcgactccat catcgatcta atagatgaat 35880 atattacgtg gagaaatcat gttatagtgt ttaacaaaga tattaccagt tgtggaagac 35940 tgtacaagga attgatgaag ttcgatgatg tcgctatacg gtactatggt attgataaaa 36000 ttaatgagat tgtcgaagct atgagcgaag gagaccacta catcaatttt acaaaagtcc 36060 atgatcagga aagttattc gctaccatag gaatatgtgc taaaatcact gaacattggg 36120 gatacaaaaa gatttcagaa tctagattcc aatcattggg aaacattaca gatttgatga 36180 ccgacgataa tataaacatc ttgatacttt ttctagaaaa aaaattgaat tgatgatata 36240 ggggtcttca taacgcataa ttattacgtt agcattctat atccgtgtta aaaaaaatta 36300 tcctatcatg tatttgagag ttttatatgt agcaaacatg atagctgtga tgccaataag 36360 ctttagatat tcacgcgtgc tagtgttagg gatggtatta tctggtggtg aaatgtccgt 36420 tatataatct acaaaacaat catcgcatat agtatgcgat agtagagtaa acatttttat 36480 agttttact ggattcatac atcgtctacc caattcggtt ataaatgaaa ttgtcgccaa 36540 tcttacaccc aaccccttgt tatccattag tatagtatta acttcgttat ttatgtcata 36600 aactgtaaat gattttgtag atgccatatc atacatgata ttcatgtccc tattataatc 36660 attactaact ttatcacaat atatgttgat aatatctata tatgatctag tctttgtggg 36720 caactgtcta tacaagtcgt ctaaacgttg tttactcata tagtatcgaa cagccatcat 36780 tacatggtcc cgttccgttg atagataatc gagtatgtta gtggacttgt caaatctata 36840 taccatattt tctggaagtg gatatacata gtcgtgatca acattattgc tagcctcatc 36900 ttctatatcc tgtactatac cattatctat atcatctaca taatctacga tattattaca 36960 cataaacatc gacaacatac tattgtttat tatctaagtc ctgttgatcc aaacccttga 37020 tctcctctat ttgtactatc tagagattgt acttcttcca gttctggata atatatacgt 37080 tgatagatta gctgagctat tctatctcca gtatttacat taaacgtaca ttttccatta 37140 ttaataagaa tgactcctat gtttccccta taatcttcgt ctattacacc acctcctata 37200 tcaatgcctt ttagtgacag accagaccta ggagctattc taccatagca gaacttaggc 37260 atggacatac taatatctgt cttaattaac tgtctttctc ctggagggat agtataatcg 37320 taagcgctat acaaatcata tccggcagca cccggcgatt gcctagtagg agatttagct 37380 ctgttagttt ccttaacaaa tctaactggt gagttaatat tcatgttgaa cataaaacta 37440 atattttatt tcaaaattat ttaccatccc atatattcca tgaataagtg tgatgattgt 37500 acacttctat agtatctata tacgattcac gataaaatcc tcctatcaat agcagtttat 37560 tatccactat gatcaattct ggattatccc tcggataaat aggatcatct atcagagtcc 37620 atgtattgct ggattcacaa taaaattccg catttctacc aaccaagaat aaccttctac 37680 cgaacactaa cgcgcatgat ttataatgag gataataagt ggatggtcca aactgccact 37740 gatcatgatt gggtagcaaa tattctgtag ttgtatcagt ttcagaatgt cctcccatta 37800 cgtatataac attgtttatg gatgccactg ctggattaca tctaggtttc agaagactcg 37860 gcatattaac ccaagcagca tccccgtgga accaacgctc aacagatgtg ggatttggta 37920 gacctcctac tacgtataat ttatgttag cgggtatccc gctagcatac agtctggggc 37980 tattcatcgg aggaattgga atccaattgt ttgatatata atttacagct atagcattgt 38040 tatgtatttc attgttcatc catccaccga tgagatatac tacttctcca acatgagtac 38100 ttgtacacat atggaatata tctataattt gatccatgtt cataggatac tctatgaatg 38160 gatacttgta tgatttgcgt ggttgtttat cacaatgaaa tattttggta cagtctagta 38220 tccattttac attatttata cctctggggag aaagataatt tgacctgatt acatttttga 38280 taaggagtag cagatttcct aatttatttc ttcgcctcat ataccactta atgacaaaat 38340 caactacata atcctcatct ggaacattta gttcatcgct ttctagaata agtttcatag 38400 atagataatc aaaattgtct atgatgtcat cttccagttc caaaaagtgt ttggcaataa 38460 agtttttagt atgacataag agattggata gtccgtattc tatacccatc atgtaacact 38520 cgacacaata ttcctttcta aaatctcgta agataaagtt tatacaagtg tagatgataa 38580 attctacaga ggttaatata gaagcacgta ataaattgac gacgttatga ctatctatat 38640 atacctttcc agtatacgag taaataacta tagaagttaa actgtgaatg tcaaggtcta 38700 gacaaaccct tgtaactgga tctttatttt tcgtgtattt ttgacgtaaa tgtgtgcgaa 38760 agtaaggaga taactttttc aatatcgtag aattgactat tatattgcca cctatagcat 38820 caataattgt tttgaatttc ttagtcatag acaatgctaa tatattctta cagtacacag 38880 tattgacaaa tatcggcatt tatgtttctt taaaagtcaa catctagaga aaaatgatta 38940 tctttttgag acataactcc cattttttgg tattcaccca cacgtttttc gaaaaaatta 39000 gtttttcctt ccaatgatat attttccatg aaatcaaacg gattggtaac attataaatt 39060 tttttaaatc ccaattcaga aatcaatcta tccgcgacga attctatata tgttttcatc 39120 atttcacaat tcattcctat aagtttaact ggaagagccg cagtaagaaa ttcttgttca 39180 atggatactg catctgttat aatagatcta acggtttctt cactcggtgg atacaataaa 39240 tgtttaaaca tcaaacatgc gaaatcgcag tgcagaccct cgtctctact aattagttcg 39300 ttggaaaacg tgagtccggg cattaggcca cgctttttaa gccaaaatat ggaagcgaat 39360 gatccggaaa agaagattcc ttctactgca gcaaaggcaa taagtctctc tccataaccg 39420 gcgctgtcat gtatccactt ttgagcccaa tcggccttct tttttacaca aggcatcgtt 39480 tctatggcat taaagagata gtttttttca ttactatctt taacataagt atcgatcaaa 39540 agactataca tttccgaatg aatgttttca atggccatct gaaatccgta gaaacatcta 39600 gcctcggtaa tctgtacttc tgtacaaaat cgttccgcca aattttcatt cactattccg 39660 tcactggctg caaaaaacgc caatacatgt tttataaaat atttttcgtc tggtgttagt 39720 ttattccaat cattgatatc tttagatata tctacttctt ccactgtcca aaatgatgcc 39780 tctgcctttt tatacatgtt ccagatgtca tgatattgga ttgggaaaat aacaaatcta 39840 tttggatttg gtgcaaggat gggttccata actaaattaa caataacaat aaattttttt 39900 tcagttatct atatgcctgt acttggatct tttgtacatc gatatcgccg caatcactac 39960 aataattaca agtattattg atagcattgt tattagtact atcataatta aattatcgac 40020 attcatgggt gctgaataat cgttattatc atcattatca ttttgtaatt gtgacatcat 40080 actagataaa tcgtttgcga gattgttgtg ggaagcgggc atggaggatg cattatcatt 40140 attatttaac gccttccatt tggattcaca aatgttacgc acattcaaca ttttatggaa 40200 actataattt tgtgaaaaca gataacaaga aaactcgtca tcgttcaaat ttttaacgat 40260 agtaaaccga ttaaacgtcg agctaatttc taacgctagc gactctgttg gatatgggtt 40320 tccaaatata tatcttttca gttcccctac gtatctataa tcatctgtag gaaatggaag 40380 atatttccat ttatctactg ttcctaatat catatgtggt ggtgtagtag aaccattaag 40440 cgcgaaagat gttatttcgc atcgtatttt aacttcgcaa taatttctgg ttagataacg 40500 cactctacca gtcaagtcaa tgatattagc ctttacagat atattcatag tagtcgtaac 40560 gatgactcca tcttttagat gcgatactcc tttgtatgta ccagaatctt cgtacctcaa 40620 actcgatata tttaaacaag ttaatgagat attaacgcgt tttatgaatg atgatatata 40680 accagaagtt ttatcctcgg tggctagcgc tataacctta tcattataat accaactagt 40740 gtgattaata tgtgacacgt cagtgtgggt acaaatatgt acattatcgt ctacgtcgta 40800 ttcgatacat ccgcatacag ccaacaaata taaaatgaca aatactctaa cgacgttcgt 40860 acccatcttg atgcggttta ataaatgttt tgatttcaat ttattgtaaa aaaagattcg 40920 gttttatact gttcgatatt ctcattgctt atattttcat ctatcatctc cacacagtca 40980 aatccgtggt tagcatgcac ctcatcaacc ggtaaaagac tatcggactc ttctatcatt 41040 ataactctag aatatttaat ttggtcatta ttaatcaagt caattatctt atttttaaca 41100 aacgtgagta ttttactcat tttttataaa aacttttaga aatatacaga ctctatcgtg 41160 tgtctatatc ttctttttat atccaatgta tttatgtctg atttttcttc atttatcata 41220 tataatggtc caaattctac acgtgcttcg gattcatcca gatcattaag gttcttataa 41280 ttgtaacatc cttctcttcc ctcttctaca tcttccttct tattcttatt cttagcgtca 41340 cagaatctac cacagcagga tcccatgacg agcgtcatat taaactaatc cattttcaat 41400 tataatatat gattagtaat gaccattaaa ataaaaaata ttcttcataa ccggcaagaa 41460 agtgaaaagt tcacattgaa actatgtcag tagtatacat catgaaatga tgatatatat 41520 atactctatt ttggtggagg attatatgat ataattcgtg gataatcatt tttaagacac 41580 atttctttat tcgtaaatct tttcacgtta aatgagtgtc catattttgc aatttcttca 41640 tatgatggcg gtgtacgtgg acgaggctgc tcctgttctt gttgtggtcg ccgactgtcg 41700 tgtctgcgtt tagatccctc cattatcgcg attgcgtaga tggagtacta ttttatacct 41760 tgtaattaaa ttttttatt aattaaacgt ataaaaacgt tccgtatctg tatttaagag 41820 ccagatttcg tctaatagaa caaatagcta cagtaaaaat aactagaata attgctacac 41880 ccactagaaa ccacggatcg taatacggca atcggttttc gataataggt ggaacgtata 41940 ttttatttaa ggacttaaca attgtctgta aaccacaatt tgcttccgcg gatcctgtat 42000 taactatctg taaaagcata tgttgaccgg gcggagccga acattctccg atatctaatt 42060 tctgtatatc tataatatta ttaacctccg catacgcatt acagttcttt tctagcttgg 42120 ataccgcact aggtacatcg tctagatcta ttcctatttc ttcagcgata gctcttctat 42180 ccttttccgg aagcaatgaa atcacttcaa taaatgattc aaccatgagt gtgaaactaa 42240 gtcgagaatt actcatgcat ttgttagtta ttcggagcgc gcaattttta aactgtccta 42300 taacctctcc tatatgaata gcacaagtga cattagtagg gatagaatgt tgagctaatt 42360 tttgtaaata actatctata aaaagattat acaaagtttt aaactcttta gtttccgcca 42420 tttatccagt ctgagaaaat gtctctcata ataaattttt ccaagaaact aattgggtga 42480 agaatggaaa cctttaatct atatttatca cagtctgttt tggtacacat gatgaattct 42540 tccaatgccg tactaaattc gatatctttt tcgatttctg gatatgtttt taataaagta 42600 tgaacaaaga aatggaaatc gtaataccag ttatgttcaa ctttgaaatt gttttttatt 42660 ttcttgttaa tgattccagc cacttgggaa aagtcaaagt cgtttaatgc cgatttaata 42720 cgttcattaa aaacaaactt tttatccttt agatgaatta ttattggttc attggaatca 42780 aaaagtaaga tattatcggg tttaagatct gcgtgtaaaa agttgtcgca acagggtagt 42840 tcgtagattt taatgtataa cagagccatc tgtaaaaaga taaactttat gtattgtacc 42900 aaagatttaa atcctaattt gatagctagc tcggtatcta ctttatctgc cgaatacagt 42960 gctaggggaa aaattataat gtttcctctt tcatattcgt agttagttct cttttcatgt 43020 tcgaaaaagt gaaacatgcg gttaaaatag tttataacat taatattact gttaataact 43080 gccggataaa agtgggatag taatttcacg aatttgatac tgtcctttct ctcgttaaac 43140 gcctttaaaa aaactttaga agaatatctc aatgagagtt cctgaccatc catagtttgt 43200 atcaataata gcaacatatg aagaacccgt ttatacagag tatgtaaaaa tgttaattta 43260 tagtttaatc ccatggccca cgcacacacg attaattttt tttcatctcc ctttagattg 43320 ttgtatagaa atttgggtac tgtgaactcc gccgtagttt ccatgggact atataatttt 43380 gtggcctcga atacaaattt tactacatag ttatctatct taaagactat accatatcct 43440 cctgtagata tgtgataaaa atcgtcgttt ataggataaa atcgtttatc cttttgttgg 43500 aaaaaggatg aattaatgta atcattctct tctatcttta gtagtgtttc cttattaaaa 43560 ttcttaaaat aatttaacaa tctaactgac ggagcccaat tttggtgtaa atctaattgg 43620 gacattatat tgttaaaata caaacagtct cctaatataa cagtatctga taatctatgg 43680 ggagacatcc attgatattc aggggatgaa tcattggcaa cacccattta ttgtacaaaa 43740 agccccaatt tacaaacgaa agtccaggtt tgatagagac aaacaattaa ctattttgtc 43800 tctgttttta acacctccac agtttttaat ttctttggta atgaaattat tcacaatatc 43860 agtatcttct ttatctacca gagattttac taacttgata accttggctg tctcattcaa 43920 tagggtagta atatttgtat gtgtgatatt gatatctttt tgaattgttt cttttagaag 43980 tgattctttg atggtgccag catacgaatt acaataatgc agaaactcgg ttaacatgca 44040 ggaattatag taagccaatt ccaattgttg cctgtgttgt attagagtgt caatatgagc 44100 aatggtgtcc ttgcgtttct ctgatagaat gcgagcagcg attttggcgt tatcatttga 44160 cgatatttct ggaatgacga atcctgtttc tactaacttt ttggtaggac aaagtgaaac 44220 aatcaagaag atagcttctc ctcctatttg tggaagaaat tgaactcctc tagatgatct 44280 actgacgata gtatctcctt gacagatatt ggaccgaatt acagaagtac ctggaatgta 44340 aagccctgaa accccctcat tttttaagca gattgttgcc gtaaatcctg cactgtgacc 44400 aagatagaga gctcctttgg tgaatccatc tctatgtttc agtttaacca agaaacagtc 44460 agctggtcta aaatttccat ctctatctaa tacagcatct aacttgatgt caggaactat 44520 gaccggttta atgttatatg taacattgag taaatcctta agttcataat catcactgtc 44580 atcagttatg tacgatccaa acaatgtttc taccggcata gtggatacga agatgctatc 44640 catcagaatg tttccctgat tagtattttc tatatagcta ttcttcttta aacgattttc 44700 caaatcagta actatgttca tttttttagg agtaggacgc ctagccagta tggaagagga 44760 tttctagat cctctcttca acatctttga tctcgatgga atgcaaaacc ccatagtgaa 44820 acaaccaacg ataaaaataa tattgttttt cactttttat aattttacca tctgactcat 44880 ggattcatta atatctttat aagagctact aacgtataat tctttataac tgaactgaga 44940 tatatacacc ggatctatgg tttccataat tgagtaaatg aatgctcggc aataactaat 45000 ggcaaatgta tagaacaacg aaattatact agagttgtta aagttaatat tttctatgag 45060 ctgttccaat aaattatttg ttgtgactgc gttcaagtca taaatcatct tgatactatc 45120 cagtaaaccg tttttaagtt ctggaatatt atcatcccat tgtaaagccc ctaattcgac 45180 tatcgaatat cctgctctga tagcagtttc aatatcgacg gacgtcaata ctgtaataaa 45240 ggtggtagta ttgtcatcat cgtgataaac tactggaata tggtcgttag taggtacagt 45300 aactttacac aacgcgatat ataactttcc ttttgtacca tttttaacgt agttgggacg 45360 tcctgcaggg tattgttttg aagaaatgat atcgagaaca gatttgatac gatatttgtt 45420 ggattcctga ttattcacta taatataatc tagacagata gatgattcga taaatagaga 45480 aggtatatcg ttggtaggat aatacatccc cattccagta ttctcggata ctctattgat 45540 gacactagtt aagaacatgt cttctattct agaaaacgaa aacatcctac atggactcat 45600 taaaacttct aacgctcctg attgtgtctc gaatgcctcg tacaaggatt tcaaggatgc 45660 catagattct ttgaccaacg atttagaatt gcgtttagca tctgattttt ttattaaatc 45720 gaatggtcgg ctctctggtt tgctacccca atgataacaa tagtcttgta aagataaacc 45780 gcaagaaaat ttatacgcat ccatccaaat aaccctagca ccatcggatg atattaatgt 45840 attattatag attttccatc cacagttatt gggccagtat actgttagca acggtatatc 45900 gaatagatta ctcatgtaac ctactagaat gatagttcgt gtactagtca taatatcttt 45960 aatccaatct aagaaattta aaattagatt ttttacactg ttaaagttaa caaaggtatt 46020 acccggatac gtggatatca tatatggcat tggtccatta tcagtaatag ctccataaac 46080 tgatacggcg atggttttta tatgtgtttg atctaacgag gaagaaattc gcgcccacaa 46140 ttcatctcta gatatgtatt taatatcaaa cggtaacaca tcaatttcgg gacgcgtata 46200 tgtttctaaa tttttaatcc aaatataatg atgacctata tgccctatta tcatactgtc 46260 aactatagta cacctaggga acttacgata catctgtttc ctgtaatcgt taaattttac 46320 aaatctataa catgctaaac cttttgacga cagccattca ttaatttctg atatggaatc 46380 tgtattctca ataccgtatc gttctaaagc cagtgctata tctccctgtt cgtgggaacg 46440 ctttcgtata atatcgatca acggataatc tgaagttttt ggagaataat atgactcatg 46500 atctatttcg tccataaaca atctagacat aggaattgga ggcgatgatc ttaattttgt 46560 gcaatgagtc gtcaatccta taacttctaa tcttgtaata ttcatcatcg acataatact 46620 atctatgtta tcatcgtata ttagtatacc atgaccttct tcatttcgtg ccaaaatgat 46680 atacagtctt aaatagttac gcaatatctc aatagtttca taattgttag ctgttttcat 46740 caaggtttgt atcctgttta acatgatggc gttctataac gtctctattt tctatttttt 46800 aaatttttaa cgatttactg tggctagata cccaatctct ctcaaatatt tttttagcct 46860 cgcttacaag ctgtttatct atactattaa aactgacgaa tccgtgattt tggtaatggg 46920 ttccgtcgaa atttgccgaa gtgatatgaa catattcgtc gtcaactatc aacaattttg 46980 tattattctg aatagtgaaa accttcacag atagatcatt ttgaacacac aacgcatcta 47040 gacttttggc ggttgccata gaatatacgt cgttcttatc ccaattacca actagaagtc 47100 tgatcttaac tcctctatta atggctgctt ctataatgga gttgtaaatg tcgggccaat 47160 agtagctatt accgtcgaca cgtgtagtgg gaactatggc caaatgttca atatctatac 47220 tagtcttagc tgacctgagt ttatcaataa ctacatcggt atctagatct ctagaatatc 47280 ccaataggtg ttccggagaa tcagtaaaga acactccacc tataggattc ttaatatgat 47340 acgcagtgct aactggcaaa caacaagccg cagagcataa attcaaccat gaattttttg 47400 cgctattaaa ggctttaaaa gtatcaaatc ttctacgaag atctgtggcc agcgggggat 47460 aatcagaata tacacctaac gttttaatcg tatgtataga tcctccagta aatgacgcgt 47520 ttcctacata acatctttca tcatctgaca cccaaaaaca accgagtagt agtcccacat 47580 tatttttttt atctatatta acggttataa aatttatatc cgggcagtga ctttgtagct 47640 ctcccagatt tcttttccct cgttcatcta gcaaaactat tattttaatc cctttttcag 47700 atgcctcttt tagtttatca aaaataagcg ctcccctagt cgtactcaga ggattacaac 47760 aaaaagatgc tatgtatata tatttcttag ctagagtgat aatttcgtta aaacattcaa 47820 atgttgtcaa atgatcggat ctaaaatcca tattttctgg tagtgtttct accagcctac 47880 attttgctcc cgcaggtacc gatgcaaatg gccacattta gttaacataa aaacttatac 47940 atcctgttct atcaacgatt ctagaatatc atcggctata tcgctaaaat tttcatcaaa 48000 gtcgacatca caacctaact cagtcaatat attaagaagt tccatgatgt catcttcgtc 48060 tatttctata tccgtatcca ttgtagattg ttgaccgatt atcgagttta aatcattact 48120 aatactcaat ccttcagaat acaatctgtg tttcattgta aatttatagg cggtgtattt 48180 aagttggtag attttcaatt atgtatcaat atagcaacag tagttcttgc tcctccttga 48240 ttctagcatc ctcttcatta ttttcttcta cgtacataaa catgtccaat acgttagaca 48300 acacaccgac gatggcggcc gccacagaca cgaatatgac taaaccgatg accatttaaa 48360 aacccctctc tagctttcac ttaaactgta tcgatcattc ttttagcaca tgtataatat 48420 aaaaacatta ttctatttcg aatttaggct tccaaaaatt tttcatccgt aaaccgataa 48480 taatatatat agacttgtta atagtcggaa taaatagatt aatgcttaaa ctatcatcat 48540 ctccacgatt agagatacaa tatttacatt ctttttgctg tttcgaaact ttatcaatac 48600 acgttaatac aaacccagga aggagatatt gaaactgagg ctgttgaaaa tgaaacggtg 48660 aatacaataa ttcagataat gtaaaatcat gattccgtat tctgatgata ttagaactgc 48720 taatggatgt cgatggtatg tatctaggag tatctatttt aacaaagcat cgatttgcta 48780 atatacaatt atccttttga ttaattgtta tttattcat attcttaaaa ggtttcatat 48840 ttatcaattc ttctacatta aaaatttcca tttttaattt atgtagcccc gcaatactcc 48900 tcattacgtt tcattttttg tctataatat ccattttgtt catctcggta catagattat 48960 ccaattgaga agcgcattta gtagttttgt acattttaag tttatgacg aatcgtcgaa 49020 aactagttat agttaacatt ttattattg ataccctgat attaataccc ctgccgttac 49080 tattatttat aactgatgta acccacgtaa cattggaatt aattatcgat agtaatgcat 49140 cgacgcttcc aaaattgtct attataaact caccgataat ttttttatta catgttttca 49200 tattcattag gattatcaaa tctttaatct tattacgatt gtatgcgttg atattacaag 49260 acgtcattct aaaagacgga ggatttccat caaatgccag acaatcacgt acaaagtaca 49320 tggaaatagg ttttgttcta ttgcgcatca tagatttata tagaacaccc gtagaaatac 49380 taatttgttt tactctataa aatactaatg catctatttc atcgttttgt ataacgtctt 49440 tccaagtgtc aaattccaaa tttttttcat tgatagtacc aaattcttct atctctttaa 49500 ctacttgcat agataggtaa ttacagtgat gcctacatgc cgttttttga aactgaatag 49560 atgcgtctag aagcgatgct acgctagtca caatcaccac tttcatattt agaatatata 49620 tatgtaaaaa tatagtagaa tttcattttg ttttttctat gctataaatg aattctcatt 49680 ttgcatctgc tcatactccg ttttatatca ataccaaaga aggaagatat ctggttctaa 49740 aagccgttaa agtatgcgat gttagaactg tagaatgcga aggaagtaaa gcttcctgcg 49800 tactcaaagt agataaaccc tcatcgcccg cgtgtgagag aagaccttcg tccccgtcca 49860 gatgcgagag aatgaataac cctggaaaac aagttccgtt tatgaggacg gacatgctac 49920 aaaatatgtt cgcggctaat cgcgataatg tagcttctag acttttgtcc taaaatacta 49980 ttatatcctt ttcgatatta ataaatccgt gtcgcccggg ttttttatct ctttcagtat 50040 gtgaatagat aggtatttta tctctattca tcatcgaatt taagagatcc gataaacatt 50100 gtttgtattc tccagatgtc agcatctgat acaacaatat atgtgcacat aaacctctgg 50160 cacttatttc atgtaccttc cccttatcac taaggagaat agtatttgag aaatatgtat 50220 acatgatatt atcatgaatt agatatacag aatttgtaac actctcgaaa tcacacgatg 50280 tgtcggcgtt aagatctaat atatcactcg ataacacatt ttcatctaga tacactagac 50340 attttttaaa gctaaaatag tctttagtag tgacagtaac tatgcgatta ttttcatcga 50400 tgatacattt catcggcata ttattacgct taccatcaaa gactatacca tgtgtatatc 50460 taacgtattc tagcatggtt gccatacgcg cattaaactt ttcaggatct ttggatagat 50520 cttccaatct atctatttga gaaaacattt ttatcatgtt caatagttga aacgtcggat 50580 ccactatata gatattatct ataaagattt taggaactac gttcatggta tcctggcgaa 50640 tattaaaact atcaatgata tgattatcgt tttcatcttt tatcaccata tagtttctaa 50700 gatatgggat tttacttaat ataatattat ttcccgtgat aaattttatt agaaaggcca 50760 aatctataag aaaagtccta gaattagtct gaagaatatc tatatcgccg tatagtatat 50820 ttggattaat tagatataga gaatatgatc cgtaacatat acaactttta ttatggcgtc 50880 taagatattc ttccatcaac ttattaacat ttttgactag ggaagataca ttatgacgtc 50940 ccattacttt tgccttgtct attactgcga cgttcataga atttagcata tctcttgcca 51000 attcttccat tgatgttaca ttataagaaa ttttagatga aattacattt ggagctttaa 51060 tagtaagaac tcctaatatg tccgtgtatg tggtcactaa tacagattgt agttctataa 51120 tcgtaaataa tttacctata ttatatgttt gagtctgttt agaaaagtag ctaagtatac 51180 gatcttttat ttctgatgca gatgtatcaa catcggaaaa aaatcttttt ttattctttt 51240 ttactaaaga tacaaatatg tctttgttaa aaacagttat tttctgaata tttctagctt 51300 gtaattttaa catatgatat tcgttcacac taggtactct gcctaaatag gtttctataa 51360 tctttaatgt aatattagga aaagtattct gatcaggatt cctattcatt ttgaggattt 51420 aaaactctga ttattgtcta atatggtctc tacgcaaact ttttcacaga gcgatagagt 51480 ttttgataac tcgtttttct taagaaatat aaaactactg tttccagagc tcgctctatc 51540 tttatttta tctaattcga tacaaactcc tgatactggt tcagaaagta attcattaat 51600 tttcagtcct ttatagaaga tatttaatat agataataca aaatcttcag tttttgatat 51660 cgatctgatt gatcctagaa ctagatatat taataacgtg ctcattaggc agtttatggc 51720 agcttgataa ttagatatag tatattccag ttcatattta ttagataccg cattgcccag 51780 attttgatat tctatgaatt cctctgaaaa taaatccaaa ataactagac attctatttt 51840 ttgtggatta gtgtactctc ttccctctat catgttcact actggtgtcc acgatgataa 51900 atatctagag ggaatataat atagtccata ggatgccaat ctagcaatgt cgaataactg 51960 taatttgatt cttcgttctt cattatgaat tgattcttga ggtataaacc taacacaaat 52020 tatattatta gacttttcgt atgtaatgtc tttcatgtta taagttttta atcctggaat 52080 agaatctatt ttaatgaggc ttttaaacgc agagttctcc aacgagtcaa agcataatac 52140 tctgttgttt ttcttatata cgatgttacg atttcttct ttgaatggaa taggtttttg 52200 aattagttta taattacaac ataatagata aggaagtgtg caaatagtac gcggaaaaaa 52260 cataatagct cccctgtttt catccatggt tttaagtaaa tgatcactgg cttctttagt 52320 caatggatat tcgaacatta accgtttcat catcattgga cagaatccat atttcttaat 52380 gtaaagagtg atcaaatcat tgtgtttatt gtaccatctt gttgtaaatg tgtattcggt 52440 tatcggatct gctccttttt ctattaaagt atcgatgtcg atctcgtcta agaattcaac 52500 tatatcgaca tatttcattt gtatacacat aaccattact aacgtagaat gtataggaag 52560 agatgtaacg ggaacagggt ttgttgattc gcaaactatt ctaatacata attcttctgt 52620 taatacgtct tgcacgtaat ctattataga tgccaagata tctatataat tattttgtaa 52680 gatgatgtta actatgtgat ctatataagt agtgtaataa ttcatgtatt tcgatatatg 52740 ttccaactct gtctttgtga tgtctagttt cgtaatatct atagcatcct caaaaaatat 52800 attcgcatat attcccaagt cttcagttct atcttctaaa aaatcttcaa cgtatggaat 52860 ataataatct attttacctc ttctgatatc attaatgata taatttttga cactatcttc 52920 tgtcaattga ttcttattca ctatatctaa gaaacggata gcgtccctag gacgaactac 52980 tgccattaat atctctatta tagcttctgg acataattca tctattatac cagaattaat 53040 gggaactatt ccgtatctat ctaacatagt tttaagaaag tcagaatcta agacctgatg 53100 ttcatatatt ggttcataca tgaaatgatc tctattgatg atagtgacta tttcattctc 53160 tgaaaattgg taactcattc tatatatgct ttccttgttg atgaaggata gaatatactc 53220 aatagaattt gtaccaacaa actgttctct tatgaatcgt atatcatcat ctgaaataat 53280 catgtaaggc atacatttaa caattagaga cttgtctcct gttatcaata tactattctt 53340 gtgataattt atgtgtgagg caaatttgtc cacgttcttt aattttgtta tagtagatat 53400 caaatccaat ggagctacag ttcttggctt aaacagatat agtttttctg gaacaaattc 53460 tacaacatta ttataaagga ctttgggtag ataagtggga tgaaatccta ttttaattaa 53520 tgcgatagcc ttgtcctcgt gcagatatcc aaacgctttt gtgatagtat ggcattcatt 53580 gtctagaaac gctctacgaa tatctgtgac agatatcatc tttagagaat atactagtcg 53640 cgttaatagt actacaattt gtatttttta atctatctca ataaaaaaat taatatgtat 53700 gattcaatgt ataactaaac tactaactgt tattgataac tagaatcaga atctaatgat 53760 gacgtaacca agaagtttat ctactgccaa tttagctgca ttatttttag catctcgttt 53820 agattttcca tcggccttat cgaatactct tccgtcgata tctacacagg cataaaatgt 53880 aggagagtta ctaggcccaa ctgattcaat acgaaaagac caatctctct tagttattg 53940 gcagtactca ttaataatgg tgacagggtt agcatctttc caatcaataa tttttttagc 54000 cggaataaca tcatcaaaag acttatgatc ctctctcatt gatttttcgc gggatacatc 54060 atctattatg acgtcagcca tagcatcagc atccggctta tccgcctccg ttgtcataaa 54120 ccaacgagga ggaatatcgt cggagctgta caccatagca ctacgttgaa gatcgtacag 54180 agctttatta acttctcgct tctccatatt aagttgtcta gttagttgtg cagcagtagc 54240 tccttcgatt ccaatggttt taatagcctc acacacaatc tctgcgttag aacgttcgtc 54300 gatatagatt ttagacattt ttagagagaa ctaacgcaac cagcaataaa actgaaccta 54360 ctttatcatt ttttattca tcatcctctg gtggttcgtc gtttctatca aatgtagctc 54420 tgattaaccc gtcatctata ggtgatgctg gttctggaga ttctggagga gatggattat 54480 tatctggaag aatctctgtt atttccttgt tttcatgtat cgattgcgtt gtaacattaa 54540 gattgcgaaa tgctctaaat ttgggaggct taaagtgttg tttgcaatct ctacacgcgt 54600 gtctaactag tggaggttcg tcagctgctc tagtttgaat catcatcggt gtagtattcc 54660 tacttttaca gttaggacac ggtgtattgt atttctcgtc aagaacgtta aaataatcgt 54720 tgtaactcac atcctttatt ttatctatat tgtattctac tcctttctta atgcatttta 54780 taccgaataa gagatagcga aggaattctt tttcggtgcc gctagtaccc ttaatcatat 54840 cacatagtgt tttatattcc aaatttgtgg caatagacgg tttatttcta tacgatagtt 54900 tgtttctgga atcctttgag tattctatac caatattatt ctttgattcg aatttagttt 54960 cttcgatatt agattttgta ttacctatat tcttgatgta gtactttgat gatttttcca 55020 tggcccattc tattaagtct tccaagttgg catcatccac atattgtgat agtaattctc 55080 ggatatcagt agcggctacc gccattgatg tttgttcatt ggatgagtaa ctactaatgt 55140 atacattttc catttataac acttatgtat taactttgtt catttatatt ttttcattat 55200 tatgttgata ttaacaaaag tgaatatata tatgttaata attgtattgt ggttatacgg 55260 ctacaatttt ataatgagtg aaagtcagtg tccgatgatc aatgacgata gctttactct 55320 gaaaagaaag tatcaaatcg atagtgcgga gtcaacaata aaaatggata agaagaggat 55380 aaagtttcag aatagagcca aaatggtaaa agaaataaat cagacaataa gagcagcaca 55440 aactcattac gagacattga aactaggata cataaaattt aagagaatga ttatgactac 55500 tactctagaa gatatagcac catctattcc aaataatcag aaaacttata aactattctc 55560 ggacatttca gccatcggca aagcatcaca gaatccgagt aagatggtat atgctctgct 55620 gctttacatg tttcccaatt tgtttggaga tgatcataga ttcattcgtt atagaatgca 55680 tccaatgagt aaaatcaaac acaagatctt ctctcctttc aaacttaatc ttattagaat 55740 attagtgggaa gaaagattct ataataatga atgcagatct aataaatgga aaataattgg 55800 aacacaagtt gataaaatgt tgatagctga atctgataaa tatacaatag atgcaaggta 55860 taacctaaaa cccatgtata gaatcaaggg agaatctgaa gaagataccc tctttatcaa 55920 acagatggta gaacaatgtg tgacatccca ggaattggtg gaaaaagtgt tgaagatact 55980 gtttagagat ttgttcaaga gtggagaata caaagcgtac agatacgatg atgatgtaga 56040 aaatggattt attggattgg atacactaaa attaaacatt gttcatgata tagttgaacc 56100 atgtatgcct gttcgtaggc cagtggctaa gatactgtgt aaagaaatgg taaataaata 56160 ctttgagaat ccgctacata ttattggtaa aaatcttcaa gagtgcattg actttgttag 56220 tgaataggca tttcatcttt ctccaatact aattcaaatt gttaaattaa taatggatag 56280 tataaatagt tattagtgat aaaatagtaa aaataattat tagaataaga gtgtagtatc 56340 atagataact ctcttctata aaaatggatt ttattcgtag aaagtatctt atatacacag 56400 tagaaaataa tatagatttt ttaaaggatg atacattaag taaagtaaac aattttaccc 56460 tcaatcatgt actagctctc aagtatctag ttagcaattt tcctcaacac gttatacta 56520 aggatgtatt agctaatacc aatttttttg ttttcataca tatggtacga tgttgtaaag 56580 tgtacgaagc ggttttacga cacgcatttg atgcacccac gttgtacgtt aaagcattga 56640 ctaagaatta tttatcgttt agtaacgcaa tacaatcgta caaggaaacc gtgcataaac 56700 taacacaaga tgaaaaattt ttagaggttg ccgaatacat ggacgaatta ggagaactta 56760 taggcgtaaa ttatgactta gttcttaatc cattatttca cggaggggaa cccatcaaag 56820 atatggaaat cattttttta aaactgttta agaaaacaga cttcaaagtt gttaaaaaat 56880 taagtgttat aagattactt atttgggcat acctaagcaa gaaagataca ggcatagagt 56940 ttgcggataa tgatagacaa gatatataca ctctatttca acaaactggt agaatcgtcc 57000 atagcaatct aacagaaacg tttagagatt atatctttcc cggagataag actagctatt 57060 gggtgtggtt aaacgaaagt atagctaatg atgcggatat cgttcttaat agacccgcca 57120 ttaccatgta tgataaaatt cttagttata tatactctga gataaaacaa ggacgcgtta 57180 ataaaaacat gcttaagtta gtttatatct ttgagcctga aaaagatatc agagaacttc 57240 tgctagaaat catatatgat attcctggag atatcctatc tattattgat gcaaaaaacg 57300 acgattgggaa aaaatatttt attagttttt ataaagctaa ttttattaac ggtaatacat 57360 ttattagtga tagaacgttt aacgaggact tattcagagt tgttgttcaa atagatcccg 57420 aatatttcga taatgaacga attatgtctt tattctctac gagtgctgcg gacattaaac 57480 gatttgatga gttagatatt aataacagtt atatatctaa tataatttat gaggtgaacg 57540 atatcacatt agatacaatg gatgatatga agaagtgtca aatctttaac gaggatacgt 57600 cgtattatgt taaggaatac aatacatacc tgtttttgca cgagtcggat cccatggtca 57660 tagagaacgg aatactaaag aaactgtcat ctataaaatc caagagtaga cggctgaact 57720 tgtttagcaa aaacatttta aaatattatt tagacggaca attggctcgt ctaggtcttg 57780 tgttagatga ttataaagga gacttgttag ttaaaatgat aaaccatctt aagtctgtgg 57840 aggatgtatc cgcattcgtt cgattttcta cagataaaaa ccctagtatt ctttcatcgc 57900 taatcaaaac tattttagct agttataata tttccatcat cgtcttattt caaaggtttt 57960 tgagagataa tctatatcat gtagaagaat tcttggataa aagcatccat ctaaccaaga 58020 cggataagaa atatatactt caattgataa gacacggtag atcatagaac agaccaaata 58080 tattattaat aatttgtata tacatagata taattatcac acatttttga taaatgggaa 58140 ctgctgcaac aattcagact cccaccaaat taatgaataa agaaaatgca gaaatgattt 58200 tggaaaaaat tgttgatcat atagttatgt atattagtga cgaatcaagt gattcagaaa 58260 ataatcctga atatattgat tttcgtaaca gatacgaaga ctatagatct ctcattataa 58320 aaagtgatca cgagtttgta aagctatgta aaaatcatgc ggagaaaagt tctccagaaa 58380 cgcaacaaat gattatcaaa cacatatacg aacaatatct tattccagta tctgaagtac 58440 tattaaaacc tataatgtcc atgggtgaca taattacata taacggatgt aaagacaatg 58500 aatggatgct agaacaactc tctaccctaa actttaacaa tctccgcaca tggaactcat 58560 gtagcatagg caatgtaacg cgtctgtttt atacattttt tagttatctg atgaaagata 58620 aactaaatat ataagtataa tcccattcta atactttaac ctgatgtatt agcatcttat 58680 tagaatatta acctaactaa aagacataac ataaaaactc attacatagt tgataaaaag 58740 cggtaggata taaatattat ggctgccacc gttccgcgtt ttgacgacgt gtacaaaaat 58800 gcacaaagaa gaattctaga tcaagaaaca ttttttagta gaggtctaag tagaccgtta 58860 atgaaaaaca catatctatt tgataattac gcgtatggat ggataccaga aactgcaatt 58920 tggagtagta gatacgcaaa cctagatgct agtgactatt atcccatttc gttgggatta 58980 cttaaaaagt tcgagtttct catgtctcta tataaaggtc ctattccagt atacgaagaa 59040 aaagtaaata ctgaattcat agccaatgga tcgttctccg gtagatacgt atcatatctt 59100 cgaaagtttt ctgctcttcc aacaaacgag tttattagtt ttttgttatt gacctccatc 59160 cctatctata atatcttgtt ctggtttaaa aatactcagt ttgatattac taaacacaca 59220 ttattcagat acgtctatac agataatgcc aaacacctgg cgttggctag gtatatgcat 59280 caaacaggag actataagcc tttgtttagt cgtctcaaag agaattatat atttaccggt 59340 cccgttccaa taagtatcaa agatatagat caccctaatc ttagtagagc aagaagtcca 59400 tccgattatg agacattagc taatattagt actatattgt actttaccaa gtatgatccg 59460 gtattaatgt ttttattgtt ttacgtacct gggtattcaa ttactacaaa aattactcca 59520 gccgtagaat atctaatgga taaactgaat ctaacaaaga gcgacgtaca actgttgtaa 59580 attattttat gcttcgtaaa atgtaggttt tgaaccaaac attctttcaa agaatgagat 59640 gcataaaact ttattatcca atagatgac tatttcggac gtcaatcgtt taaagtaaac 59700 ttcgtaaaat attctttgat cactgccgag tttaaaactt ctatcgataa ttgtttcata 59760 tgttttaata tttacaagtt ttttggtcca tggtacatta gccggacaaa tatatgcaaa 59820 ataatatcgt tctccaagtt ctatagtttc tggattattt ttattatatt cagtaaccaa 59880 atacatatta gggttatctg cggatttata atttgagtga tgcattcgac tcaacataaa 59940 taattctaga ggagacgatc tactatcaaa ttcggatcgt aaatctgttt ctaaagaacg 60000 gagaatatct atacatacct gattagaatt catccgtcct tcagacaaca tctcagacag 60060 tctggtcttg tatgtcttaa tcatattctt atgaaacttg gaaacatctc ttctagtttc 60120 actagtacct ttattaattc tctcaggtac agattttgaa ttcgacgatg ctgagtattt 60180 catcgttgta tatttcttct tcgattgcat aatcagattc ttatataccg cctcaaactc 60240 tattttaaaa ttattaaaca atactctatt attaatcagt cgttctaact ctttcgctat 60300 ttctatagac ttatcgacat cttgactgtc tatctctgta aacacggagt cggtatctcc 60360 atacacgcta cgaaaacgaa atctgtaatc tataggcaac gatgttttca caatcggatt 60420 aatatctcta tcgtccatat aaaatggatt acttaatgga ttggcaaacc gtaacatacc 60480 gttagataac tctgctccat ttagtaccga ttctagatac aagatcattc tacgtcctat 60540 ggatgtgcaa ctcttagccg aagcgtatga gtatagagca ctatttctaa atcccatcag 60600 accatatact gagttggcta ctatcttgta cgtatattgc atggaatcat aaatggcctt 60660 ttcagttgaa ctggtagcct gttttagcat ctttttatat ctggctctct ctgccaaaaa 60720 tgttcttaat agtctaggaa tggttccttc tatcgatcta tcgaaaattg ctatttcaga 60780 gatgaggttc ggtagtctag gttcacaatg aaccgtaata tatctaggag gtggatattt 60840 ctgaagcaag agctgattat ttatttcttc ttccaatcta ttggtactaa caacgacacc 60900 gactaatgtt tccggagata gatttccaaa gatacacaca ttaggataca gactgttata 60960 atcaaagatt aatacattat tactaaacat tttttgtttt ggagcaaata ccttaccgcc 61020 ttcataagga aacttttgtt ttgtttctga tctaactaag atagttttag tttccaacaa 61080 tagctttaac agtggaccct tgatgactgt actcgctcta tattcgaata ccatggattg 61140 aggaagcaca tatgttgacg cacccgcgtc tgtttttgtt tctactccat aatactccca 61200 caaatactga cacaaacaag catcatgaat acagtatcta gccatatcta aagctatgtt 61260 tagattataa tccttataca tctgagctaa atcaacgtca tcctttccga aagataattt 61320 atatgtatca ttaggtaaag taggacataa tagtacgact ttaaatccat tttcccaaat 61380 atctttacga attactttac atataatatc ctcatcaaca gtcacataat tacctgtggt 61440 taaaaccttt gcaaatgcag cggctttgcc tttcgcgtct gtagtatcgt caccgatgaa 61500 cgtcatttct ctaactcctt tatttaatac tttacccatg caactgaacg cgttcttgga 61560 tatagaatcc aatttgtacg aatccaattt ttcaaatttt tgaatgaatg aatatagatc 61620 gaaaaatata gttccattat tgttattaac gtgaaacgta gtattggcca tgccgcctac 61680 tcccttatga ctagactgat ttctctcata aatacagaga tgtacagctt cctttttgtc 61740 cggagatcta aagataatct tctctcctgt taataactct agacgattag taatatatct 61800 cagatcaaag ttatgtccgt taaaggtaac gacgtagtcg aacgttagtt ccaacaattg 61860 tttagctatt cgtaacaaaa ctatttcaga acatagaact agttctcgtt cgtaatccat 61920 ttccattagt gactgtatcc tcaaacatcc tctatcgacg gcttcttgta tttcctgttc 61980 cgttaacatc tcttcattaa tgagcgtaaa caataatcgt ttaccactta aatcgatata 62040 acagtaactt gtatgcgaga ttgggttaat aaatacagaa ggaaacttct tatcgaagtg 62100 acactctata tctagaaata agtacgatct tgggatatcg aatctaggta tttttttagc 62160 gaaacagtta cgtggatcgt cacaatgata acatccattg ttaatctttg tcaaatattg 62220 ctcgtccaac gagtaacatc cgtctggaga tatcccgtta gaaatataaa accaactaat 62280 attgagaaat tcatccatgg tggcattttg tatgctgcgt ttctttggct cttctatcaa 62340 ccacatatct gcgacggagc attttctatc tttaatatct agattataac ttattgtctc 62400 gtcaatgtct atagttctca tctttcccaa cggcctcgca ttaaatggag gaggagacaa 62460 tgactgatat atttcgtccg tcactacgta ataaaagtaa tgaggaaatc gtataaatac 62520 ggtctcgcca tttcgacatc tggatttcag atataaaaat ctgttttcac cgtgactttc 62580 aaaccaatta atgcaccgaa catccattta tagaatttag aaatatattt tcatttaaat 62640 gaatcccaaa cattggggaa gagccgtatg gaccattatt tttatagtac tttcgcaagc 62700 gggtttagac ggcaacatag aagcgtgtaa acgaaaacta tatactatag ttagcactct 62760 tccatgtcct gcatgtagac ggcacgcgac tatcgctata gaggacaata atgtcatgtc 62820 tagcgatgat ctgaattata tttattattt tttcatcaga ttatttaaca atttggcatc 62880 tgatcccaaa tacgcgatcg atgtgacaaa ggttaaccct ttataaactt aacccattat 62940 aaaacttatg attagtcaca actgaaataa ccgcgtgatt attttttggt ataattctac 63000 acggcatggt ttctgtgact atgaattcaa cccccgttac attagtgaaa tctttaacaa 63060 acagcaaggg ttcgtcaaag acataaaact cattgtttac aatcgaaata gaccccctat 63120 cacacttaaa ataaaaata tccttatcct ttaccaccaa ataaaattct gattggtcaa 63180 tgtgaatgta ttcacttaac agttccacaa atttatttat taactccgag gcacatacat 63240 cgtcggtatt ttttatggca aactttactc ttccagcatc cgtttctaaa aaaatattaa 63300 cgagttccat ttatatcatc caatattatt gaaataacgt tgatggacag atgatacaaa 63360 taagaaggta cggtaccttt gtccaccatc tcctccaatt catgctctat tttgtcatta 63420 actttaatgt atgaaaacag tacgccacat gcttccatga cagtgtgtaa cactttggat 63480 acaaaatgtt tgacattagt atatgtcc aagactgtca atctataata gatagtagct 63540 ataatatatt ctatgatggt attgaagaag atgacaacct tggcatattg atcatttaac 63600 acagacatgg tatcaacaga tagcttgaat gaaagagaat cagtaattgg aataagcgtc 63660 ttctcgatag agtgtccgta taccaacatg tctgatattt tgatgtattc cattaaatta 63720 tttagttttt tctttttatt ttcgttaaac agcatttctg tcaacggacc ccaacatcgt 63780 tgaccaatta agttttgatt gatttttccg tgtaaggcgt atctagtcag atcgtatagc 63840 ctatccaata atccatcgtc tgtgtgtaga tcacatcgta cactttttaa ttctctatag 63900 aagagcgaca gacatctgga gcaattacag acagcaattt ctttattctc tacagatgta 63960 agatacttga agacattcct atgatgatgc agaattttgg ataacacggt attgatggta 64020 tctgttacca taattccttt gatggctgat agtgtcagag cacaagattt ccaatctttg 64080 acaattttta gcaccattat ctttgttttg atatctatat cagacagcat ggtgcgtctg 64140 acaacacagg gattaagacg gaaagatgaa atgattctct caacatcttc aatggatacc 64200 ttgctatttt ttctggcatt atctatatgt gcgagaatat cctctagaga atcagtatcc 64260 tttttgatga tagtggatct caatgacatg ggacgtctaa accttcttat tctatcacca 64320 gattgcatgg tgatttgtct tctttctttt atcataatgt aatctctaaa ttcatcggca 64380 aattgtctat atctaaaatc ataatatgag atgtttacct ctacaaatat ctgttcgtcc 64440 aatgttagag tatttacatc agttttgtat tccaaattaa acatggcaac ggatttaatt 64500 ttatattcct ctattaagtc ctcgtcgata ataacagaat gtagataatc atttaatcca 64560 tcgtacatgg ttggaagatg cttgttgaca aaatctttaa ttgtcttgat gaaggtggga 64620 ctatatctaa catcttgatt aataaaattt ataacattgt ccataggata ctttgtaact 64680 agttttatac acatctcttc atcggtaagt ttagacagaa tatcgtgaac aggtggtata 64740 ttatattcat cagatatacg aagaacaatg tccaaatcta tattgtttaa tatattatat 64800 agatgtagcg tagctcctac aggaatatct ttaactaagt caatgatttc atcaaccgtc 64860 agatctattt taaagttaat catataggca ttgattttta aaaggtatgt agccttgact 64920 acattctcat taattaacca ttccaagtca ctgtgtgtaa gaagattata ttctatcata 64980 agcttgacta catttggtcc cgataccatt aaagaattct tatgatataa ggaaacagct 65040 tttaggtact catctactct acaagaattt tggagagcct taacgatatc agtgacgttt 65100 attatttcag gaggaaaaaa cctaacattg agaatatcgg aattaatagc ttccagatac 65160 agtgattttg gcaatagtcc gtgtaatcca taatccagta acacgagctg gtgcttgcta 65220 gacacctttt caatgtttaa tttttttgaa ataagctttg ataaagcctt cctcgcaaat 65280 tccggataca tgaacatgtc ggcgacatga ttaagtattg ttttttcatt attttctcaa 65340 caagttctca ataccccaat agatgataga atatcaccca atgcgtccat gttgtctatt 65400 tccaacaggt cgctatatcc accaatagaa gtttttccaa aaaagattct aggaacagtt 65460 ctaccaccag taatttgttc aaaatagtcc cgcaattcat tttcgggttt aaattcttta 65520 atatcgacaa tttcatacgc tcctcttttg aaactaaact tatttagaat atccagtgca 65580 tttctacaaa aaggacatgt aaacttgaca aaaattgtca ctttgttatt ggccaacctt 65640 tgttgtacaa attcctcggc cattttaata tttaagtgat ataaaactat ctcgacttat 65700 ttaactcttt agtcgagata tatggacgca gatagctata tgatagccaa ctacagaagg 65760 caaacgctat aaaaacata attacgacga gcatatttat aaatattttt attcagcatt 65820 acttgatata gtaatattag gcacagtcaa acattcaacc actctcgata cattaactct 65880 ctcattttct ttaacaaatt ctgcaatatc ttcgtaaaaa gattcttgaa actttttaga 65940 atatctatcg actctagatg aaatagcgtt cgtcaacata ctatgttttg tatacataaa 66000 ggcgcccatt ttaacagttt ctagtgacaa aatgctagcg atcctaggat cctttagaat 66060 cacatagatt gacgattcgt ctctcttagt aactctagta aaataatcat acaatctagt 66120 acgcgaaata atattatcct tgacttgagg agatctaaac aatctagttt tgagaacatc 66180 gataagttca tcgggaatga catacatact atctttaata gaactctttt catccagttg 66240 aatggattcg tccttaacca actgattaat gagatcttct attttatcat tttccagatg 66300 atatgtatgt ccattaaagt taaattgtgt agcgcttctt tttagtctag cagccaatac 66360 tttaacatca ctaatatcga tatacaaagg agatgattta tctatggtat taagaattcg 66420 tttttcgaca tccgtcaaaa ccaattcctt tttgcctgta tcatccagtt ttccatcctt 66480 tgtaaagaaa ttattttcta ctagactatt aataagactg ataaggattc ctccataatt 66540 gcacaatcca aactttttca caaaactaga ctttacgaga tctacaggaa tgcgtacttc 66600 aggtttttta gcttgtgatt ttttcttttg cggacatttt ctagtaacca actcatctac 66660 catttcattg attttagcag tgaaataagc tttcaatgca cgggcactga tactattgaa 66720 aacgagttga tcttcaaatt ccgccattta agttcaccaa acaactttta aatacaaata 66780 tatcaatagt agtagaataa gaactataaa aaaaataata attaaccaat accaacccca 66840 acaaccggta ttattagttg atgtggtagt tttctcatca cttagaacag atttaacaat 66900 ttctataaag tctgtcaaat catcttccgg agaccccata aatacaccaa atatagcggc 66960 gtacaactta tccatttata cattgaatat tggcttttct ttatcgctat cttcatcata 67020 ttcatcatca atatcaacaa gtcccagatt acgagccaga tcttcttcta cattttcagt 67080 cattgataca cgttcactat ctccagagag tccgataacg ttagccacca cttctctatc 67140 aatgattagt ttcttgagcg cgaatgtaat ttttgtttcc gttccggatc tatagaagac 67200 gataggtgtg ataattgcct tggccaattg tctttctctt ttactgagtg attctagttc 67260 accttctata gatctgagaa tggatgattc tccagtcgaa acatattcta ccatggatcc 67320 gtttaatttg ttgatgaaga tggattcatc cttaaatgtt ttctctgtaa tagtttccac 67380 cgaaagacta tgcaaagaat ttggaatgcg ttccttgtgc ttaatgtttc catagacggc 67440 ttctagaagt tgatacaaca taggactagc cgcggtaact tttatttta gaaagtatcc 67500 atcgcttcta tcttgtttag atttattttt ataaagttta gtctctcctt ccaacataat 67560 aaaagtggaa gtcatttgac tagataaact atcagtaagt tttatagaga tagacgaaca 67620 attagcgtat tgagaagcat ttagtgtaac gtattcgata cattttgcat tagatttact 67680 aatcgatttt gcatactcta taacacccgc acaagtctgt agagaatcgc tagatgcagt 67740 aggtcttggt gaagtttcaa ctctcttctt gattacctta ctcatgatta aacctaaata 67800 attgtacttt gtaatataat gatatatatt ttcactttat ctcatttgag aataaaaatg 67860 tttttgttta accactgcat gatgtacaga tttcggaatc gcaaaccacc agtggtttta 67920 ttttatcctt gtccaatgtg aattgaatgg gagcggatgc gggtttcgta cgtagatagt 67980 acattcccgt ttttagaccg agactccatc cgtaaaaatg catactcgtt agtttggaat 68040 aactcggatc tgctatatgg atattcatag attgactttg atcgatgaag gctcccctgt 68100 ctgcagccat ttttatgatc gtcttttggg gaatttccca aatagtttta taaactcgct 68160 taatatcttc tggaaggttt gtattctgaa tggatccacc atctgccata atcctattct 68220 tgatctcatc attccataat tttctctcgg ttaaaactct aaggagatgc ggattaacta 68280 cttgaaattc tccagacaat actctccgag tgtaaatatt actggtatac ggttccaccg 68340 actcattatt tcccaaaatt tgagcagttg atgcagtcgg cataggtgcc accaataaac 68400 tatttctaag accgtatgtt ctgattttat cttttagagg ttcccaattc caaagatccg 68460 acggtacaac attccaaaga tcatattgta gaataccgtt actggcgtac gatcctacat 68520 atgtatcgta tggtccttcc ttctcagcta gttcacaact cgcctctaat gcaccgtaat 68580 aaatggtttc gaagatcttc ttatttagat cttgtgcttc caggctatca aatggataat 68640 ttaagagaat aaacgcgtcc gctaatcctt gaacaccaat accgataggt ctatgtctct 68700 tattagat ttcagcttct ggaataggat aataattaat atctataatt ttattgagat 68760 ttctgacaat tactttgacc acatccttca gtttgagaaa atcaaatcgc ccatctatta 68820 caaacatgtt caaggcaaca gatgccagat tacaaacggc tacctcatta gcatccgcat 68880 attgtattat ctcagtgcaa agattactac acttgatagt tcctaaattt tgttgattac 68940 tctttttgtt acacgcatcc ttataaagaa tgaatggagt accagtttca atctgagatt 69000 ctataatcgc tttccagacg actcgagcct ttattataga tttgtatctc ctttctcttt 69060 cgtatagtgt atacaatcgt tcgaactcgt ctccccaaac attgtccaat ccaggacatt 69120 catccggaca catcaacgac cactctccgt catccttcac tcgtttcata aagagatcag 69180 gaatccaaag agctataaat agatctctgg ttctatgttc ctcgtttcct gtattctttt 69240 taagatcgag gaacgccata atatcagaat gccacggttc caagtatatg gccataactc 69300 caggccgttt gtttcctccc tgatctatgt atctagcggt gttattataa actctcaaca 69360 ttggaataat accgtttgat ataccattgg taccggagat atagcttcca ctggcacgaa 69420 tattactaat tgatagacct attccccctg ccattttaga gattaatgcg catcgtttta 69480 acgtgtcata gataccctct atgctatcat cgatcatgtt aagtagaaaa cagctagaca 69540 tttggtgacg actagttccc gcattaaata aggtaggaga agcgtgcgta aaccattttt 69600 cagaaagtag attgtacgtc tcaatagctg agtctatatc ccattgatga attcctactg 69660 cgacacgcat taacatgtgc tgaggtcttt caacgatctt gttgtttatt ttcaacaagt 69720 aggatttttc caaagtttta aaaccaaaat agttgtatga aaagtctcgt tcgtaaataa 69780 taaccgagtt gagtttatcc ttatatttgt taactatatc catggtgata cttgaaataa 69840 tcggagaatg tttcccattt ttaggattaa catagttgaa taaatcctcc atcacttcac 69900 taaatagttt ttttgtttcc ttgtgtagat ttgatacggc tattctggcg gctagaatgg 69960 cataatccgg atgttgtgta gtacaagtgg ctgctatttc ggctgccaga gtgtccaatt 70020 ctaccgttgt tactccatta tatattcctt gaataacctt catagctatt ttaataggat 70080 ctatatgatc cgtgtttaag ccataacata attttctaat acgagacgtg attttatcaa 70140 acatgacatt ttccttgtat ccatttcgtt taatgacaaa catttttgtt ggtgtaataa 70200 aaaaattatt taacttttca ttaataggga tttgacgtat gtagcgtaca aaattatcgt 70260 tcctggtata tagataaaga gtcctatata tttgaaaatc gttacggctc gattaaactt 70320 taatgattgc atagtgaata tatcattagg atttaactcc ttgactatca gggcggcacc 70380 agaaattacc atcaaaagca ttaatacagt tatgccgatc gcagttagaa cggttatagc 70440 atccaccatt tatatctaaa aattagatca aagaatatgt gacaaagtcc tagttgtata 70500 ctgagaattg acgaaacaat gtttcttaca tatttttttc ttattagtaa ctgacttaat 70560 agtaggaact ggaaagctag acttgattat tctataagta tagataccct tccaaataat 70620 attctctttg ataaaagttc cagaaaatgt agaatttttt aaaaagttat cttttgctat 70680 taccaagatt gtgtttagac gcttattatt aatatgagtg atgaaatcca caccgcctct 70740 agatatcgct tttatttcca cattagatgg taaatccaat agtgaaacta tctttttagg 70800 aatgtatgga ctcgcgttta gaggagtgaa cgtcttaggc gtcggaaagg atgattcatc 70860 aaacgaataa acaatttcac aaatggatgt taatgtatta gtaggaaatt ttttgacgct 70920 agtggaattg aagattctaa tggatgatgt tctacctatt tcatccgata acatgttaat 70980 ttccgacacc aacggtttta atatttcgat gatatacggt agtctctctt tcggacttat 71040 atagcttatt ccacaatacg agtcattata tactccaaaa aacaaaataa ctagtataaa 71100 atctgtatcg aatgggaaaa acgaaattat cgacataggt atagaatctg gaacattgaa 71160 cgtattaata cttaattctt tttctgtggt aagtaccgat aggttatga cattgtatgg 71220 ttttaaatat tctataactt gagacttgat agatattagt gatgaattga aaattatttt 71280 tatcaccacg tgtgtttcag gatcatcgtc gacgcccgtc aaccaaccga atggagtaaa 71340 ataaatatca ttaatatatg ctctagatat tagtattttt atcaatcctt tgattatcat 71400 cttctcgtag gcgaatgatt ccatgatcaa gagtgattta agaacatcct ccggagtatt 71460 aatgggctta gtaaacagtc catcgttgca ataataaaag ttatccaagt taaaggatat 71520 tatgcattcg tttaaagata tcacctcatc tgacggagac aattttttgg taggttttag 71580 agactttgaa gctacttgtt taacaaagtt attcatcgtc gtttactatt ctatttaatt 71640 ttgtagttaa tttatcacat atcacattaa ttgacttttt ggtccatttt tccatacgtt 71700 tatattcttt taatcctgcg ttatccgttt ccgttatatc cagggataga tcttgcaagt 71760 taaatagaat gctcttaaat aatgtcattt ttttatccgc taaaaattta aagaatgtat 71820 aaactttttt caaagattta aaacttttag gtggagttct agtacacaat atcataaaca 71880 aactaataaa catcccgcat tcagattcca acagctgatt aacttccaca ttaatacagc 71940 ctattttcgc tccaaatgta cattcgaaaa atctgaataa aacatcgatg tcacaatttg 72000 tattatccaa tacagaatgt ctgtgattcg tgttaaaacc atcggagaag gaatagaaat 72060 aaaaattatt atagtggtgg aattcagttg gaatattgcc tccggagtca taaaaggata 72120 ctaaacattg ttttttatca taaattacac atttccaatg agacaaataa caaaatccaa 72180 acattacaaa tctagaggta gaacttttaa ttttgtcttt aagtatatac gataagatat 72240 gttattcat aaacgcgtca aatttttcat gaatcgctaa ggaggtttaag aatctcatgt 72300 caaattgtcc tatataatcc acttcggatc cataagcaaa ctgagagact aagttcttaa 72360 tacttcgatt gctcatccag gctcctctct caggctctat tttcatcttg acgacctttg 72420 gattttcacc agtatgtatt cctttacgtg ataaatcatc gattttcaaa tccatttggg 72480 agaagtctat cgccttagat actttttccc gtagtcgagg tttaaagaaa tacgctaacg 72540 gtatactagt aggtaactca aagacatcat atatagaatg gtaacgcgtc tttaactcgt 72600 cggttaactc tttcttttga tcgagttcgt cgctactatt gggtctgctc aggtgccccg 72660 actctactag ttccaacatc ataccgatag gaatacaaga cactttgcca gcggttgtag 72720 atttatcata tttctccact acatatccgt tacaatttgt taaaaattta gatacatcta 72780 tattgctaca taatccagct agtgaatata tatgacataa taaattggta aatcctagtt 72840 ctggtatttt actaattact aaatctgtat atctttccat ttatcatgga aaagaattta 72900 ccagatatct tcttttttcc aaactgcgtt aatgtattct cttacaaata ttcacaagat 72960 gaattcagta atatgagtaa aacggaacgt gatagtttct cattggcggt gtttccagtt 73020 ataaacata gatggcataa cgcacacgtt gtaaaacata aaggaatata caaagttagt 73080 acagaagcac gtggaaaaaa agtatctcct ccatcactag gaaaacccgc acacataaac 73140 ctaaccgcga agcaatatat atacagtgaa cacacaataa gctttgaatg ttatagtttt 73200 ctaaaatgta taacaaatac agaaatcaat tcgttcgatg agtatatatt aagaggacta 73260 ttagaagctg gtaatagttt acagatattt tccaattccg taggtaaacg aacagatact 73320 ataggtgtac tagggaataa gtatccattt agcaaaattc cattggcctc attaactcct 73380 aaagcacaac gagagatattttcagcgtgg atttctcata gacctgtagt tttaactgga 73440 ggaactggag tgggtaagac gtcacaggta cccaagttat tgctttggtt taattattta 73500 tttggtggat tctctactct agataaaatc actgactttc acgaaagacc agtcattcta 73560 tctcttccta ggatagcttt agttagattg catagcaata ccattttaaa atcattggga 73620 tttaaggtac tagatggatc tcctatttct ttacggtacg gatctatacc ggaagaatta 73680 ataaacaaac aaccaaaaaa atatggaatt gtattttcta cccataagtt atctctaaca 73740 aaactattta gttatggcac tcttattata gacgaagttc atgagcatga tcaaatagga 73800 gatattatta tagcagtagc gagaaagcat catacgaaaa tagattctat gtttttaatg 73860 actgccacgt tagaggatga cagggaacgg ctaaaagtat ttttacctaa tcccgcattt 73920 atacatattc ctggagatac actgtttaaa attagcgagg tatttattca taataagata 73980 aatccatctt ccagaatggc atacatagaa gaagaaaaga gaaatttagt tactgctata 74040 cagatgtata ctcctcctga tggatcatcc ggtatagtct ttgtggcatc cgttgcacag 74100 tgtcacgaat ataaatcata tttagaaaaa agattaccgt atgatatgta tattattcat 74160 ggtaaggtct tagatataga cgaaatatta gaaaaagtgt attcatcacc taatgtatcg 74220 ataattattt ctactcctta tttggaatcc agcgttacta tacacaatgt tacacacatt 74280 tatgatatgg gtagagtttt tgtccccgct ccttttggag gatcgcaaga atttatttct 74340 aaatctatga gagatcaacg aaaaggaaga gtaggaagag ttaatcctgg tacatacgtc 74400 tatttctatg atctgtctta tatgaagtct atacagcgaa tagattcaga atttctacat 74460 aattatat tgtacgctaa taagtttaat ctaacactcc ccgaagattt gtttataatc 74520 cctacaaatt tggatattct atggcgtaca aaggaatata tagactcgtt cgatattagt 74580 acagaaacat ggaataaatt attatccaat tattatatga agatgataga gtatgctaaa 74640 ctttatgtac taagtcctat tctcgctgag gagttggata actttgagag gacgggagaa 74700 ttaactagta ttgtacgaga agccatttta tctctaaatt tacgaattaa gattttaaat 74760 tttaaacata aagatgatga tacgtatata cacttttgta aaatattatt cggtgtctat 74820 aacggaacaa acgctactat atattatcat agacctctaa cgggatatat gaatatgatt 74880 tcagatacta tatttgttcc tgtagataat aactaaaaat caaactctaa tgaccacatc 74940 tttttttaga gatgaaaaat tttctacatc tccttttgta gacacgacta aacattttgc 75000 agaaaaaagt ttattagtgt ttagataatc gtatacttca tcagtgtaga tagtaaatgt 75060 gaacagataa aaggtattct tgctcaatag attggtaaat tccatagaat atattaatcc 75120 tttcttcttg agatcccaca tcatttcaac cagagacgtt ttatccaatg atttacctcg 75180 tactatacca catacaaaac tagattttgc agtgacgtcg tacctggtat tcctaccaaa 75240 caaaatttta cttttagttc ttttagaaaa ttctaaggta gaatctctat ttgccaatat 75300 gtcatctatg gaattacac tagcaaaaaa tgatagaaat atatattgat acatcgcagc 75360 tggttttgat ctactatact ttaaaaacga atcagattcc ataattgcct gtatatcatc 75420 agctgaaaaa ctatgtttta cacgtattcc ttcggcattt ctttttaatg atatatcttg 75480 tttagacaat gataaagtta tcatgtccat gagagacgcg tctccgtatc gtataaatat 75540 ttcattagat gttagacgct tcattaggggg tatacttcta taaggtttct taatcagtcc 75600 atcattggtt gcgtcaagaa ctactatcgg atgttgttgg gtatctctag tgttacacat 75660 ggccttaacta aagtttgggt aaataactat gatatctcta ttaattatag atgcatatat 75720 ttcatttgtc aaggattatta gtatcgactt gctatcgtca ttaatacgtg taatgtaatc 75780 atataaatca tgcgatagcc aaggaaaatt taaatagatg ttcatcatat aatcgtcgct 75840 ataattcata ttaatacgtt gacattgact aatttgtaat atagcctcgc cacgaagaaa 75900 gctctcgtat tcagtttcat cgataaagga taccgttaaa tataactggt tgccgatagt 75960 ctcatagtct attaagtggt aagtttcgta caaatacaga atccctaaaa tattatctaa 76020 tgttggatta atctttacca taactgtata aaatggagac ggaggtcataa ctattttacc 76080 gtttgtactt actggaatag atgaaggaat aatctccgga catgctggta aagacccaaa 76140 tgtctgtttg aagaaatcca atgttccagg tcctaatctc ttaacaaaaa ttacgatatt 76200 cgatcccgat atcctttgca ttctatttac cagcatatca cgaactatat taagattatc 76260 tatcatgtct attctcccac cgttatataa atcgcctccg ctaagaaacg ttagtatatc 76320 catacaatgg aatacttcat ttctaaaata gtattcgttt tctaattctt taatgtgaaa 76380 tcgtatacta gaaagggaaa aattatcttt gagttttccg ttagaaaaga accacgaaac 76440 taatgttctg attgcgtccg attccgttgc tgaattaatg gatttacacc aaaaactcat 76500 ataacttcta gatgtagaag cattcgctaa aaaattagta gaatcaaagg atataagtag 76560 atgttccaac aagtgagcaa ttcccaagat ttcatctata tcattctcga atccgaaatt 76620 agaaattccc aagtagatat cctttttcat ccgatcgttg atgaaaatac gaactttatt 76680 cggtaagaca atcatttaact aaggagtaaa ataggaagta atgttcgtat gtcgttatca 76740 tcgtataaat taaaggtgtg ttttttacca ttaagtgaca ttataatttt accaatattg 76800 gaattataat ataggtgtat ttgcgcactc gcgacggttg atgcatcggt aaatatagct 76860 gtatctaatg ttctagtcgg tatttcatca tttcgctgtc taataatagc gttttctcta 76920 tctgtttcca ttacagctgc ctgaagttta ttggtcggat aatatgtaaa ataataagaa 76980 atacatacga ataacaaaaa taaaataaga tataataaag atgccattta gagatctaat 77040 tttgtttaac ttgtccaaat tcctacttac agaagatgag gaatcgttgg agatagtgtc 77100 ttccttatgt agaggatttg aaatatctta tgatgacttg ataacttact ttccagatag 77160 gaaataccat aaatatattt ctaaagtatt tgaacatgta gatttatcgg aggaattaag 77220 tatggaattc catgatacaa ctctgagaga tttagtctat cttagattgt acaagtattc 77280 caagtgtata cggccgtgtt ataaattagg agataatcta aaaggcatag ttgttataaa 77340 ggacaggaat atttatatta gagaagcaaa tgatgacttg atagaatatc tcctcaagga 77400 atacactcct cagatttata catattctaa tgagcgcgtc cccataactg gttcaaaatt 77460 aattctttgt ggattttctc aagttacatt tatggcgtat acaacgtcgc atataacaac 77520 aaataaaaag gtagatgttc tcgtttccaa aaaatgtata gatgaactag tcgatccaat 77580 aaattatcaa atacttcaaa atttatttga taaaggaagc ggaacaataa acaaaatact 77640 caggaagata tttattcgg taaccggtgg ccaaactcca taatttgctt tttctatttc 77700 ggattttaga atttccaaat tcaccagcga tttatcggtt ttggtgaaat ccaaggattt 77760 attaatgtcc acaaatgcca tttgttttgt ctgtggattg tatttgaaaa tggaaacgat 77820 gtagttagat agatgcgctg caaagtttcc tattagggtt ccgcgcttta cgtcacccag 77880 catacttgaa tcaccatcct ttaaaaaaaa tgataagata tcaacatgga gtatatcata 77940 ctcggatttt aattcttcta ctgcatcact gacattttca caaatactac aatacggttt 78000 accgaaaata atcagtacgt tcttcattta tgggtatcaa aaacttaaaa tcgttactgc 78060 tggaaaataa atcactgacg atattagatg ataatttata caaagtatac aatggaatat 78120 ttgtggatac aatgagtatt tatatagccg tcgccaattg tgtcagaaac ttagaagagt 78180 taactacggt attcataaaa tacgtaaacg gatgggtaaa aaagggaggg catgtaaccc 78240 tttttatcga tagaggaagt ataaaaatta aacaagacgt tagagacaag agacgtaaat 78300 attctaaatt aaccaaggac agaaaaatgc tagaattaga aaagtgtaca tccgaaatac 78360 aaaatgttac cggatttatg gaagaagaaa taaaggcaga aatgcaatta aaaatcgata 78420 aactcacatt tcaaatatat ttatctgatt ctgataacat aaaaatatca ttgaatgaga 78480 tactaacaca tttcaacaat aatgagaatg ttacattatt ttattgtgat gaacgagacg 78540 cagaattcgt tatgtgtctc gaggctaaaa cacatttctc taccacagga gaatggccgt 78600 tgataataag taccgatcag gatactatgc tatttgcatc tactgataat catcctaaga 78660 tgataaaaaa cttaactcaa ctgtttaaat ttgttccctc ggcagaggat aactatttag 78720 caaaattaac ggcgttagtg aatggatgtg atttctttcc tggactctat ggggcatcta 78780 taacacccac caacttaaac aaaatacaat tgtttagtga ttttacaatc gataatatag 78840 tcactagttt ggcaattaaa aattattata gaaagactaa ctctaccgta gacgtgcgta 78900 atattgttac gtttataaac gattacgcta atttagacga tgtctactcg tatgttcctc 78960 cttgtcaatg cactgttcaa gaatttatat tttccgcatt agatgaaaaa tggaacaatt 79020 ttaaatcatc ttaatttagag accgttccgt taccctgcca attaatgtat gcattagaac 79080 cacgcaagga gattgatgtt tcagaagtta aaactttatc atcttatata gatttcgaaa 79140 atactaaatc agatatcgat gttataaaat ctatatcttc gatcttcgga tattctaacg 79200 aaaactgtaa cactatagtg ttcggcatct ataaggataa tttaactactg agtataaata 79260 gttcatttta ctttaacgat agtctgttaa taaccaatac taaaagtgat aatataataa 79320 atataggtta ctagattaaa aatggtgttc caactcgtgt gctctacgtg cggcaaagat 79380 atttctcacg aacgatataa attgattata cgaaaaaat cattaaagga tgtactcgtc 79440 agtgtaaaga acgaatgttg taggttaaaa ttatctacac aaatagaacc tcaacgtaac 79500 ttaacagtgc aacctctatt ggatataaac taatatggat ccggttaatt ttatcaagac 79560 atatgcgcct agaggttcta ttatttttat taattatacc atgtcattaa caagtcattt 79620 gaatccatcg atagaaaaac atgtgggtat ttattatggt acgttattat cggaacactt 79680 ggtagttgaa tctacctata gaaaaggagt tcgaatagtc ccattggata gtttttttga 79740 aggatatctt agtgcaaaag tatacatgtt agagaatatt caagttatga aaatagcagc 79800 tgatacgtca ttaactttat tgggtattcc gtatggattt ggtcatgata gaatgtattg 79860 ttttaaattg gtagctgaat gttataaaaa tgccggtatt gatacatcgt ctaaacgaat 79920 attaggtaaa gatatttttc tgagccaaaa cttcacagat gataatagat ggataaagat 79980 atatgattct aataatttaa cattttggca aattgattac cttaaagggt gagttaatat 80040 gcataactac tcctccgttg ttttttccct cgttcttttt cttaacgttg tttgccatca 80100 ctctcataat gtaaagatat tctaaaatgg taaacttttg catatcggac gcagaaattg 80160 gtataaatgt tgtaattgta ttatttcccg tcaatggact agtcacagct ccatcagttt 80220 tatatccttt agagtatttc tcactcgtgt ctaacattct agagcattcc atgatctgtt 80280 tatcgttgat attggccgga aagatagatt ttttattttt tattatatta ctattggcaa 80340 ttgtagatat aacttctggt aaatattttt ctaccttttc aatctcttct attttcaagc 80400 cggctatata ttctgctata ttgttgctag tatcaatacc ttttctggct aagaagtcat 80460 atgtggtatt cactatatca gttttaactg gtagttccat tagcctttcc acttctgcag 80520 aataatcaga aattggttct ttaccagaaa atccagctac tataataggc tcaccgatga 80580 tcattggcaa aatcctatat tgtaccagat taatgagagc atatttcatt tccaataatt 80640 ctgctagttc ttgagacatt gatttatttg atgaatctag ttggttctct agatactcta 80700 ccatttctgc cgcatacaat aacttgttag ataaaatcag ggttatcaaa gtgtttagcg 80760 tggctagaat agtgggcttg catgtattaa agaatgcggt agtatgagta aaccgtttta 80820 acgaattata tagtctccag aaatctgtgg cgttacatac atgagccgaa tgacatcgaa 80880 gattgtccaa tatttttaat agctgctctt tgtccattat ttctatattt gactcgcaac 80940 aattgtagat accattaatc actgattcct ttttcgatgc cggacaatag cacaattgtt 81000 tagctttgga ctctatgtat tcagaattaa tagatatatc tctcaataca gattgcacta 81060 tacattttga aactatgtca aaaattgtag aacgacgctg ttctgcagcc atttaacttt 81120 aaataattta caaaaattta aaatgagcat ccgtataaaa atcgataaac tgcgccaaat 81180 tgtggcatat ttttcagagt tcagtgaaga agtatctata aatgtagact cgacggatga 81240 gttaatgtat atttttgccg ccttgggcgg atctgtaaac atttgggcca ttatacctct 81300 cagtgcatca gtgttctacc gcggagccga aaacattgtg tttaatcttc ctgtgtccaa 81360 ggtaaaatcg tgtttgtgta gttttcacaa tgatgccatc atagatatag aacctgatct 81420 ggaaaataat ctagtaaaac tttctagtta tcatgtagta agtgtcgatt gtaacaagga 81480 actgatgcct attaggacag atactactat ttgtctaagt atagatcaaa agaaatctta 81540 cgtgtttaat tttcacaagt atgaagaaaa atgttgtggt agaaccgtca ttcatttaga 81600 atggttgttg ggctttatca agtgattag tcagcatcag catttggcta ttatgtttaa 81660 agatgacaat attattatga agactcctgg taatactgat gcgttttcca gggaatattc 81720 tatgactgaa tgttctcaag aactacaaaa gttttctttc aaaatagcta tctcgtctct 81780 caacaaacta cgaggattca aaaagagagt caatgttttt gaaactagaa tcgtaatgga 81840 taatgacgat aacattctag gaatgttgtt ttcggataga gttcaatcct ttaagatcaa 81900 catctttatg acgtttttag attaatactt tcaatgagat aaatatgggt ggcagagtaa 81960 gtgttgagct ccctaaacgg gatccgcctc cgggagtacc cactgatgag atgttattaa 82020 acgtggataa aatgcatgac gtgatagctc ccgctaagct tttagaatat gtgcatatag 82080 gaccactagc aaaagataaa gaggataaag taaagaaaag atatccagag tttagattag 82140 tcaacacagg acccggtggt ctttcggcat tgttaagaca atcgtataat ggaaccgcac 82200 ccaattgctg tcgcactttt aatcgtactc attattggaa aaaggatgga aagatatcag 82260 ataagtatga agagggtgca gtattagaat cgtgttggcc agacgttcac gacactggaa 82320 aatgcgatgt tgatttattc gactggtgtc agggggatac gttcgataga aacatatgcc 82380 atcagtggat cggttcagcc tttaatagga gtgatagaac tgtagagggt caacaatcgt 82440 taataaatct gtataataag atgcaaacat tatgtagtaa agatgctagt gtaccaatat 82500 gtgaatcatt tttgcatcat ttacgcgcac acaatacaga agatagcaaa gagatgatcg 82560 attatattct aagacaacag tctgcggact ttaaacagaa atatatgaga tgtagttatc 82620 ccactagaga taagttagaa gagtcattaa aatatgcgga acctcgagaa tgttggggatc 82680 cagagtgttc gaatgccaat gttaatttct tactaacacg taattataat aatttaggac 82740 tttgcaatat tgtacgatgt aatactagcg tgaacaactt acagatggat aaaacttcct 82800 cattaagatt gtcatgtgga ttaagcaata gtgatagatt ttctactgtt cccgtcaata 82860 gagcaaaagt agttcaacat aatattaaac attcgttcga cctaaaattg catttgatca 82920 gtttattatc tctcttggta atatggatac taattgtagc tatttaaatg ggtgccgcgg 82980 caagcataca gacgacggtg aatacactca gcgaacgtat ctcgtctaaa ttagaacaag 83040 aagcgaacgc tagtgctcaa acaaaatgtg atatagaaat cggaaatttt tatatccgac 83100 aaaaccatgg atgtaacctc actgttaaaa atatgtgctc tgcggacgcg gatgctcagt 83160 tggatgctgt gttatcagcc gctacagaaa catatagtgg attaacaccg gaacaaaaag 83220 catacgtacc agctatgttt actgctgcgt taaacattca gacgagtgta aacactgttg 83280 ttagagattt tgaaaattat gtgaaacaga cttgtaattc tagcgcggtc gtcgataaca 83340 aattaaagat acaaaacgta atcatagatg aatgttacgg agccccagga tctccaacaa 83400 atttggaatt tattaataca ggatctagca aaggaaattg tgccattaaa gcgttgatgc 83460 aattgacgac taaggccact actcaaatag cacctagaca agttgctggt acaggagttc 83520 agttttatat gattgttatc ggtgttataa tattggcagc gttgtttatg tactatgcca 83580 agcgtatgtt gttcacatcc accaatgata aaatcaaact tattttagcc aataaggaaa 83640 acgtccattg gactacttac atggacacat tctttagaac ttctccgatg gttattgcta 83700 ccacggatat gcaaaactga aaatatattg ataatatttt aatagattaa catggaagtt 83760 atcgctgatc gtctagacga tatagtgaaa caaaatatag cggatgaaaa atttgtagat 83820 tttgttatac acggtctaga gcatcaatgt cctgctatac ttcgaccatt aattaggttg 83880 tttatgata tactattatt tgttatagta atttatattt ttacggtacg tctagtaagt 83940 agaaattatc aaatgttgtt ggtggcgcta gtcatcacat taactatttt ttattacttt 84000 atactataat agtactagac tgacttctaa caaacatctc acctgccata aataaatgct 84060 tgatattaaa gtcttctatt tctaacacta ttccatctgt ggaaaataat actctgacat 84120 tatcgctaat tgacacatcg gtgagtgata tgcctataaa gtaataatct tctttgggca 84180 catataccag tgtaccaggt tctaacaacc tatttactgg tgctcctgta gcatactttt 84240 tctttacctt gagaatatcc atcgtttgct tggtcaatag cgatatgtga ttttttatca 84300 accactcaaa aaagtaattg gagtgttcat atcctctacg ggctattgtc tcatggccgt 84360 gtatgaaatt taagtaacac gactgtggta gatttgttct atagagccgg ttgccgcaaa 84420 tagatagaac taccaatatg tctgtacaaa tgttaaacat taattgatta acagaaaaaa 84480 caatgttcgt tctgggaata gaaaccagat caaaacaaaa ttcgttagaa tatatgccac 84540 gtttatacat ggaatataaa ataactacag tttgaaaaat aacagtatca tttaaacatt 84600 taacttgcgg ggttaatttc acaactttac tgtttttaaa ctgttcaaaa tatagcatcg 84660 atccatgaga aatacgttta gccgccttta atagaggaaa tcccaccgcc tttctggatc 84720 tcaccaacga cgatagttct gaccagcaac ttatttcttc atcatccacc tgttttaaca 84780 tataataggc aggagataga tatccgtcat tgcaatattc cttttcgtag gcacacaatc 84840 taatattgat aaaatctcca ttctcttctc tgcatttat atcttgtttc ggtggctgat 84900 taggctgtag tcttggttta ggctttggta tatcgttgtt gaatctattt tggtcattaa 84960 atctttcatt tcttcctggt atatttttat cacctcgttt ggttggattt ttgtctatat 85020 tatcgtttgt aacatcggta cgggtattca tttatcacaa aaaaaacttc tctaaatgag 85080 tctactgcta gaaaacctca tcgaagaaga taccatattt tttgcaggaa gtatatctga 85140 gtatgatgat ttacaaatgg ttattgccgg cgcaaaatcc aaatttccaa gatctatgct 85200 ttctattttt aatatagtac ctagaacgat gtcaaaatat gagttggagt tgattcataa 85260 cgagaatatc acaggggcaa tgtttaccac aatgtataat ataagaaaca atttgggtct 85320 aggagatgat aaactaacta ttgaagccat tgaaaactat ttcttggatc ctaacaatga 85380 ggttatgcct cttatcatta ataatacgga tatgactgcc gtcattccta aaaaaagtgg 85440 taggagaaag aataagaaca tggttatttt ccgtcaagga tcatcaccta tcttgtgtat 85500 tttcgaaact cgtaaaaaga ttaatattta taaagaaaat atggaatccg cgtcgactga 85560 gtatacacct atcggagaca acaaggcttt gatatctaaa tatgcgggaa ttaatgtcct 85620 gaatgtgtat tctccttcca catccatgag attgaatgcc atttacggat tcaccaataa 85680 aaataaacta gagaaactta gtactaataa ggaactagaa tcgtatagtt ctagccctct 85740 tcaagaaccc attaggttaa atgattttct gggactattg gaatgtgtta aaaagaatat 85800 tcctctaaca gatattccga caaaggatg attactataa atggagaatg ttcctaatgt 85860 atactttaat cctgtgttta tagagccac gtttaaacat tctttattaa gtgtttataa 85920 acacagatta atagttttat ttgaagtatt cattgtattc attctaatat atgtattttt 85980 tagatctgaa ttaaatatgt tcttcatgcc taaacgaaaa atacccgatc ctattgatag 86040 attacgacgt gctaatctag cgtgtgaaga cgataaatta atgatctatg gattaccatg 86100 gatgacaact caaacatctg cgttatcaat aaatagtaaa ccgatagtgt ataaagattg 86160 tgcaaagctt ttgcgatcaa taaatggatc acaaccagta tctcttaacg atgttcttcg 86220 cagatgatga ttcatttttt aagtatttgg ctagtcaaga tgatgaatct tcattatctg 86280 atatattgca aatcactcaa tatctagact ttctgttatt attattgatc caatcaaaaa 86340 ataaattaga agccgtgggt cattgttatg aatctctttc agaggaatac agacaattga 86400 caaaattcac agactttcaa gattttaaaa aactgtttaa caaggtccct attgttacag 86460 atggaagggt caaacttaat aaaggatatt tgttcgactt tgtgattagt ttgatgcgat 86520 tcaaaaaaga atcctctcta gctaccaccg caatagatcc tattagatac atagatcctc 86580 gtcgcgatat cgcattttct aacgtgatgg atatattaaa gtcgaataaa gtgaacaata 86640 attaattctt tattgtcatc atgaacggcg gacatattca gttgataatc ggccccatgt 86700 tttcaggtaa aagtacagaa ttaattagac gagttagacg ttatcaaata gctcaatata 86760 aatgcgtgac tataaaatat tctaacgata atagatacgg aacgggacta tggacgcatg 86820 ataagaataa ttttgaagca ttggaagcaa ctaaactatg tgatgtcttg gaatcaatta 86880 cagatttctc cgtgataggt atcgatgaag gacagttctt tccagacatt gttgaattct 86940 gtgagcgtat ggcaaacgaa ggaaaaatag ttatagtagc cgcactcgat gggacatttc 87000 aacgtaaacc gtttaataat attttgaatc ttattccatt atctgaaatg gtggtaaaac 87060 taactgctgt gtgtatgaaa tgctttaagg aggcttcctt ttctaaacga ttgggtgagg 87120 aaaccgagat agaaataata ggaggtaatg atatgtatca atcggtgtgt agaaagtgtt 87180 acatcgactc ataatattat attttttatc taaaaaacta aaaataaaca ttgattaaat 87240 tttaatataa tacttaaaaa tggatgttgt gtcgttagat aaaccgttta tgtattttga 87300 ggaaattgat aatgagttag attacgaacc agaaagtgca aatgaggtcg caaaaaaact 87360 accgtatcaa ggacagttaa aactattact aggagaatta ttttttctta gtaagttaca 87420 gcgacacggt atattagatg gtgccaccgt agtgtatata ggatcggctc ctggtacaca 87480 tatacgttat ttgagagatc atttctataa tttaggagtg atcatcaaat ggatgctaat 87540 tgacggccgc catcatgatc ctattttaaa tggattgcgt gatgtgactc tagtgactcg 87600 gttcgttgat gaggaatatc tacgatccat caaaaaacaa ctgcatcctt ctaagattat 87660 tttaatttct gatgtaagat ccaaacgagg aggaaatgaa cctagtacgg cggatttact 87720 aagtaattac gctctacaaa atgtcatgat tagtatttta aaccccgtgg catctagtct 87780 taaatggaga tgcccgtttc cagatcaatg gatcaaggac ttttatatcc cacacggtaa 87840 taaaatgtta caaccttttg ctccttcata ttcagctgaa atgagattat taagtattta 87900 taccggtgag aacatgagac tgactcgagt taccaaatta gacgctgtaa attatgaaaa 87960 aaagatgtac taccttaata agatcgtccg taacaaagta gttgttaact ttgatttcc 88020 taatcaggaa tatgactatt ttcacatgta ctttatgctg aggacccgtgt actgcaataa 88080 aacatttcct actactaaag caaaggtact atttctacaa caatctatat ttcgtttctt 88140 aaatattcca acaacatcaa ctgaaaaagt tagtcatgaa ccaatacaac gtaaaatatc 88200 tagcaaaaat tctatgtcta aaaacagaaa tagcaagaga tccgtacgcg gtaataaata 88260 gaaacgtgct actgagatat actaccgata tagagtataa tgatttagtt actttaataa 88320 ccgttagaca taaaattgat tctatgaaaa ctgtgtttca ggtatttaac gaatcatcca 88380 taaattatac tccggttgat gatgattatg gagaaccaat cattataaca tcgtatcttc 88440 aaaaaggtca taacaagttt cctgtaaatt ttctatacat agatgtggta atatctgact 88500 tatttcctag ctttgttaga ctagatacta cagaaactaa tatagttaat agtgtactac 88560 aaacaggcga tggtaaaaag actcttcgtc ttcccaaaat gttagagacg gaaatagttg 88620 tcaagattct ctatcgccct aatataccat taaaaattgt tagatttttc cgcaataaca 88680 tggtaactgg agtagagata gccgatagat ctgttatttc agtcgctgat taatcaatta 88740 gtagagatga gataagaaca ttataataat caataatatt atcttatatc tcgtttagaa 88800 aaatgctaat attaaaatag ctaacgctag taatccaatc ggaagccatt tgatatctat 88860 aatagggtat ctaatttcct gattcagata gcggacagct atattctcgg tagctactcg 88920 tttggaatca caaacattat ttacatctaa tttactatct gtaatggaaa cgtttcccaa 88980 tgaaatggta caatccgata cattgcattt tgttattattt ttttttaaag aggctggtaa 89040 caacgcatcg cttcgtttac atggctcgta ccaacaataa tagggtaatc ttgtatctat 89100 tcctatccgt actatgcttt tatcaggata aatacattta catcgtatat cgtctttgtt 89160 agcatcacag aatgcataaa tttgttcgtc cgtcatgata aaaatttaaa gtgtaaatat 89220 aactattatt tttatagttg taataaaaag ggaaatttga ttgtatactt tcggttcttt 89280 aaaagaaact gacttgataa aaatggctgt aatctctaag gttacgtata gtctatatga 89340 tcaaaaagag attaatgcta cagatattat cattagtcat gttaaaaatg acgacgatat 89400 cggtaccgtt aaagatggta gactaggtgc tatggatggg gcattatgta aaacttgtgg 89460 gaaaacggaa ttggaatgtt tcggtcactg gggtaaagta agtatttata aaactcatat 89520 agttaagcct gaatttattt cagaaattat tcgtttactg aatcatatat gtattcactg 89580 cggattattg cgttcacgag aaccgtattc cgacgatatt aacctaaaag agttatcggg 89640 acacgctctt aggagattaa aggataaaat attatccaag aaaaagtcat gttggaacag 89700 cgaatgtatg caaccgtatc aaaaaattac tttttcaaag aaaaaggttt gtttcgtcaa 89760 caagttggat gatattaacg ttcctaattc tctcatctat caaaagttaa tttctattca 89820 tgaaaagttt tggccattat tagaaattca tcaatatcca gctaacttat tttatacaga 89880 ctactttccc atccctccgc tgattattag accggctatt agtttttgga tagatagtat 89940 acccaaagag accaatgaat taacttactt attaggtatg atcgttaaga attgtaactt 90000 gaatgctgat gaacaggtta tccagaaggc ggtaatagaa tacgatgata ttaaaattat 90060 ttctaataac actaccagta tcaatttatc atatattaca tccggcaaaa ataatatgat 90120 tagaagttat atcgtcgccc gacgaaaaga tcagaccgct agatctgtaa ttggtcccag 90180 tacatctatc accgttaatg aggtaggaat gcccgcatat attagaaata cacttacaga 90240 aaagatattt gttaatgcct ttacagtgga taaagttaaa caactattag cgtcaaacca 90300 agttaaattt tactttaata aacgattaaa ccaattaaca agaatacgcc aaggaaagtt 90360 tatcaaaaat aaaatacatt tattgcctgg tgattgggta gaagtagctg ttcaagaata 90420 tacaagtatt atttttggaa gacagccgtc tctacataga tacaacgtca tcgcttcatc 90480 tatcagagct accgaaggag atactatcaa aatatctccc ggaattgcca actctcaaaa 90540 tgctgatttc gacggagatg aagaatggat gatattggag caaaatccta aagccgtaat 90600 tgaacaaagt attcttatgt atccgacgac gttactcaaa cacgatattc atggagcccc 90660 cgtttatgga tctattcaag atgaaatcgt agcagcgtat tcattgttta ggatacaaga 90720 tctttgttta gatgaagtat tgaacatctt ggggaaatat ggaagagagt tcgatcctaa 90780 aggtaaatgt aaattcagcg gtaaagatat ctatacttac ttgataggtg aaaagattaa 90840 ttatccgggt ctcttaaagg atggtgaaat tattgcaaac gacgtagata gtaattttgt 90900 tgtggctatg aggcatctgt cattggctgg actcttatcc gatcataagt cgaacgtgga 90960 aggtatcaac tttattatca agtcatctta tgtttttaag agatatctat ctatttacgg 91020 ttttggggtg acattcaaag atctgagacc aaattcgacg ttcactaata aattggaggc 91080 catcaacgta gaaaaaatag aacttatcaa agaagcatac gccaaatatc tcaacgatgt 91140 aagagacggg aaaatagttc cattatctaa agctttagag gcggactatg tggaatccat 91200 gttatccaac ttgacaaatc ttaatatccg agagatagaa gaacatatga gacaaacgct 91260 gatagatgat ccagataata acctcctgaa aatggccaaa gcgggttata aagtaaatcc 91320 tacagaacta atgtatattc taggtacgta tggacaacaa aggattgatg gtgaaccagc 91380 agagactcga gtattgggta gagtcttacc ttactatctt ccagactcta aggatccaga 91440 aggaagaggt tacattctta attctttaac aaaaggatta acgggttctc aatattactt 91500 ttcgatgctg gttgccagat ctcaatctac tgatatcgtc tgtgaaacat cacgtaccgg 91560 aacactggct agaaaaatca ttaaaaagat ggaggatatg gtggtcgacg gatacggaca 91620 agtagttata ggtaatacgc tcatcaagta cgccgccaat tataccaaaa ttctaggctc 91680 agtatgtaaa cctgtagatc ttatctatcc agatgagtcc atgacttggt atttggaaat 91740 tagtgctctg tggaataaaa taaaacaggg attcgtttac tctcagaaac agaaacttgc 91800 aaagaagaca ttggcgccgt ttaatttcct agtattcgtc aaacccacca ctgaggataa 91860 tgctattaag gttaaggatc tgtacgatat gattcataac gtcattgatg atgtgagaga 91920 gaaatacttc tttacggtat ctaatataga ttttatggag tatatattct tgacgcatct 91980 taatccttct agaattagaa ttacaaaaga aacggctatc actatctttg aaaagttcta 92040 tgaaaaactc aattatactc taggtggtgg aactcctatt ggaattattt ctgcacaggt 92100 attgtctgag aagtttacac aacaagccct gtccagtttt cacactactg aaaaaagtgg 92160 tgccgtcaaa caaaaacttg gtttcaacga gtttaataac ttgactaatt tgagtaagaa 92220 taagaccgaa attatcactc tggtatccga tgatatctct aaacttcaat ctgttaagat 92280 taatttcgaa tttgtatgtt tgggagaatt aaatccagac atcactcttc gaaaagaaac 92340 agataaatat gtagtagata taatagttaa tagattatac atcaagagag cagaaataac 92400 cgaattagtt gtcgaatata tgattgaacg atttatctcc tttagcgtca ttgtaaagga 92460 atggggtatg gagacattca ttgaggacga ggataatatt agatttactg tctacctaaa 92520 tttcgttgaa ccggaagaat tgaatcttag taagtttatg atggttcttc cgggtgccgc 92580 caacaagggc aagattagta aattcaagat tcctatctct gattatacgg gttatgacga 92640 cttcaatcaa acaaaaaagc tcaataagat gactgtagaa ctcatgaatc taaaagaatt 92700 gggttctttc gatttggaaa acgtcaacgt gtatcctgga gtatggaata catacgatat 92760 cttcggtatc gaggccgctc gtgaatactt gtgcgaagcc atgttaaaca cctatggaga 92820 agggttcgat tatctgtatc agccttgtga tcttctcgct agtttactat gtgctagtta 92880 cgaaccagaa tcagttaata aattcaagtt cggtgcagct agtactctta agagagctac 92940 gttcggagac aataaagcat tgttaaacgc ggctcttcat aaaaagtcag aacctattaa 93000 cgataatagt agctgccact tttttagcaa ggtccctaat ataggaactg gatattacaa 93060 atactttatc gacttgggtc ttctcatgag aatggaaagg aaactatctg ataagatatc 93120 ttctcaaaag atcaaggaaa tggaagaaac agaagacttt taattcttat caataacata 93180 tttttctatg atctgtcttt taaacgatgg attttccaca aatgcgcctc tcaagtccct 93240 catagaatga tacacgtata aaaaatatag cataggcaat gactccttat ttttagacat 93300 tagatatgcc aaaatcatag ccccgcttct atttactccc gcagcacaat gaaccaacac 93360 gggctcgttt cgttgatcac atttagataa aaaggcggtt acgtcgtcaa aatatttact 93420 aatatcggta gttgtatcat ctaccaacgg tatatgaata atattaatat tagagttagg 93480 taatgtatat ttatccatcg tcaaatttaa aacatatttg aacttaactt cagatgatgg 93540 tgcatccata gcatttttat aatttcccaa atacacatta ttggttaccc ttgtcattat 93600 agtgggagat ttggctttgt gcatatctcc agttgaacgt agtagtaagt atttatacaa 93660 acttttctta tccatttata acgtacaaat ggataaaact actttatcgg taaacgcgtg 93720 taatttagaa tacgttagag aaaaggctat agtaggcgta caagcagcca aaacatcaac 93780 acttatattc tttgttatta tattggcaat tagtgcgcta ttactctggt ttcagacgtc 93840 tgataatcca gtctttaatg aattaacgag atatatgcga attaaaaata cggttaacga 93900 ttggaaatca ttaacggata gcaaaacaaa attagaaagt gatagaggta gacttctagc 93960 cgctggtaag gatgatatat tcgacttcaa atgtgtggat ttcggcgcct attttatagc 94020 tatgcgattg gataagaaaa catatctgcc gcaagctatt aggcgaggta ctggagacgc 94080 gtggatggtt aaaaaggcgg caaaggtcga tccatctgct caacaatttt gtcagtattt 94140 gataaaacac aagtctaata atgtattac ttgtggtaat gagatgttaa atgaattagg 94200 ttatagcggt tattttatgt caccgcattg gtgttccgat tttagtaata tggatagtg 94260 ttagataaat gcggtaacga atgttcctgt aaggaaccat aacagtttag atttaacgtt 94320 aaagatgagc ataaacataa taaacaaaat tacaatcaaa cctataacat taatatcaaa 94380 caatccaaaa aatgaaatca gtggagtagt aaacgcgtac ataactcctg gataacgttt 94440 agcagctgcc gttcctattc tagaccaaaa attcggtttc atgttttcga agcggtgttc 94500 tgcaacaagt cggggatcgt gttctacata tttggcggcg ttatccagta tctgcctatt 94560 gatcttcatt tcgttttcga ttctggctat ttcaaaataa aatcccgatg atagacctcc 94620 agactttata atttcatcta cgatgttcag cgccgtagta actctaataa tataggctga 94680 taagctaaca tcataccctc ctgtatatgt gaatatggca tgatttttgt ccattacaag 94740 ctcggtttta actttatgc ctgtaataat ttctctcatc tgtaggatat ctattttttt 94800 gtcatgcatt gccttcaaga cgggacgaag aaacgtaata tcctcaataa cgtttcgtt 94860 ttctacaata actacatatt ctaccttttt attttctaac tcggtaaaaa aattagaatc 94920 ccatagggct aaatgtctag cgatatttct tttcgtttcc tctgtacaca tagtgttaca 94980 aaaccctgaa aagaagtgag tatacttgtc atcatttcta atgtttcctc cagtccactg 95040 tataaacgca taatccttgt aatgatctgg atcatccttg actaccacaa catttctttt 95100 ttctggcata acttcgttgt cctttacatc atcgaacttc tgatcattaa tatgctcatg 95160 aacattagga aatgtttctg atggaggtct atcaataact ggcacaacaa taacaggagt 95220 tttcaccgcc gccatttagt tattgaaatt aatcatatac aactctttaa tacgagttat 95280 attttcgtct atccattgtt tcacatttac atatttcgac aaaaagatat aaaatgcgta 95340 ttccaatgct tctctgttta atgaattact aaaatataca aacacgtcac tgtctggcaa 95400 taaatgatat cttagaatat tgtaacaatt tattttgtat tgcacatgtt cgtgatctat 95460 gagttcttct tcgaatggca taggatctcc gaatctgaaa acgtataaat aggagttaga 95520 ataataatat ttgagagtat tggtaatata taaactcttt agcggtataa ttagtttttt 95580 tctctcaatt tctattttta gatgtgatgg aaaaatgact aattttgtag cattagtatc 95640 atgaactcta atcaaaatct taatatcttc gtcacacgtt agctctttga agtttttaag 95700 agatgcatca gttggttcta cagatggagt aggtgcaaca attttttgtt ctacacatgt 95760 atgtactgga gccattgttt taactataat ggtgcttgta tcgaaaaact ttaatgcaga 95820 tagcggaagc tcttcgccgc gactttctac atcgtaattg ggttctaacg ccgatctctg 95880 aatggatact agttttctaa gttctaatgt gattctctga aaatgtaaat ccaattcctc 95940 cggcattata gatgtgtata catcggtaaa taaaactata gtatccaacg atcccttctc 96000 gcaaattcta gtcttaacca aaaaatcgta tataaccacg gagatggcgt atttaagagt 96060 ggattcttct accgttttgt tcttggatgt catataggaa actataaagt ccgcactact 96120 gttaagaatg attactaacg caactatata gttcaaatta agcattttgg aaacataaaa 96180 taactctgta gacgatactt gactttcgaa taagtttgca gacaaacgaa gaaagaacag 96240 acctctctta atttcagaag aaaacttttt ttcgtattcc tgacgtctag agtttatatc 96300 aataagaaag ttaagaatta gtcggttaat gttgtatttc attacccaag tttgagattt 96360 cataatatta tcaaaagaca tgataatatt aaagataaag cgctgactat gaacgaaata 96420 gctatatggt tcgctcaaaa atatagtctt gttaaacgtg gaaacgataa ctgtattttt 96480 aatcacgtca gcggcatcta aattaaatat aggtatattt attccacaca ctctacaata 96540 tgccacacca tcttcataat aaataaattc gttagcaaaa ttattaattt tagtgaaata 96600 gttagcgtca actttcatag cttccttcaa tctaatttga tgctcacacg gtgcgaattc 96660 cactctaaca tcccttttcc atgcctcagg ttcatcgatc tctataatat ctagtttttt 96720 gcgtttcaca aacacaggct cgtctctcgc gatgagatct gtatagtaac tatgtaaatg 96780 ataactagat agaaagatgt agctatatag atgacgatcc tttaagagag gtataataac 96840 tttaccccaa tcagatagac tgttgttatg gtcttcggaa aaagaatttt tataaatttt 96900 tccagtattt tccaaatata cgtacttaac atctaaaaaa tccttaatga taataggaat 96960 ggataatccg tctattttat aaagaaatac atatcgcaca ttatactttt ttttggaaat 97020 gggaataccg atgtgtctac ataaatatgc aaagtctaaa tattttttag agaatcttaa 97080 ttggtccaaa ttcttttcca agtacggtaa tagatttttc atattgaacg gtatcttctt 97140 aatctctggt tctagttccg cattaaatga tgaaactaag tcactatttt tataactaac 97200 gattacatca cctctaacat catcatttac cagaatactg atcttctttt gtcgtaaata 97260 catgtctaat gtgttaaaaa aaagatcata caagttatac gtcatttcat ctgtggtatt 97320 cttgtcattg aaggataaac tcgtactaat ctcttcttta acagcctgtt caaatttata 97380 tcctatatac gaaaaaatag caaccagtgt ttgatcatcc gcgtcaatat tctgttctat 97440 cgtagtgtat aacaatcgta tatcttcttc tgtgatagtc gatacgttat aaaggttgat 97500 aacgaaaata ttttatttc gtgaaataaa gtcatcgtag gattttggac ttatattcgc 97560 gtctagtaga tatgctttta tttttggaat gatctcaatt agaatagtct ctttagagtc 97620 catttaaagt tacaaacaac taggaaattg gtttatgatg tataattttt ttagttttta 97680 tagattcttt attctatact taaaaaatga aaataaatac aaaggttctt gagggttgtg 97740 ttaaattgaa agcgagaaat aatcataaat tatttcatta tcgcgatatc cgttaagttt 97800 gtatcgtaat ggcgtggtca attacaaata aagcggatac tagtagcttc acaaagatgg 97860 ctgaaatcag agctcatcta aaaaatagcg ctgaaaataa agataaaaac gaggatattt 97920 tcccggaaga tgtaataatt ccatctacta agcccaaaac caaacgagcc actactcctc 97980 gtaaaccagc ggctactaaa agatcaacca aaaaggagga agtggaagaa gaagtagtta 98040 tagaggaata tcatcaaaca actgaaaaaa attctccatc tcctggagtc agcgacattg 98100 tagaaagcgt ggccgctgta gagctcgatg atagcgacgg ggatgatgaa cctatggtac 98160 aagttgaagc tggtaaagta aatcatagtg ctagaagcga tctctctgac ctaaaggtgg 98220 ctaccgacaa tatcgttaaa gatcttaaga aaattattac tagaatctct gcagtatcga 98280 cggttctaga ggatgttcaa gcagctggta tctctagaca atttacttct atgactaaag 98340 ctattacaac actatctgat ctagtcaccg agggaaaatc taaagttgtt cgtaaaaaag 98400 ttaaaacttg taagaagtaa atgcgtgcac ttttttataa agatggtaaa ctctttaccg 98460 ataataattt tttaaatcct gtatcagacg ataatccagc gtatgaggtt ttgcaacatg 98520 ttaaaattcc tactcattta acagatgtag tagtatatga acaaacgtgg gaggaggcgt 98580 taactagatt aatttttgtg ggaagtgatt caaaaggacg tagacaatac ttttacggaa 98640 aaatgcatgt acagaatcgc aacgctaaaa gagatcgtat ttttgttaga gtatataacg 98700 ttatgaaacg aattaattgt tttataaaca aaaatataaa gaaatcgtcc acagattcca 98760 attatcagtt ggcggttttt atgttaatgg aaactatgtt ttttattaga tttggtaaaa 98820 tgaaatatct taaggagaat gaaacagtag ggttattaac actaaaaaat aaacacatag 98880 aaataagtcc cgatgaaata gttatcaagt ttgtaggaaa ggacaaagtt tcacatgaat 98940 ttgttgttca taagtctaat agactatata agccgctatt gaaactgacg gatgattcta 99000 gtcccgaaga atttctgttc aacaaactaa gtgaacgaaa ggtatatgaa tgtatcaaac 99060 agtttggtat tagaatcaag gatctccgaa cgtatggagt caattatacg tttttatata 99120 atttttggac aaatgtaaag tccatatctc ctcttccatc accaaaaaag ttaatagcgt 99180 taactatcaa acaaactgct gaagtggtag gtcatactcc atcaatttca aaaagagctt 99240 atatggcaac gactatttta gaaatggtaa aggataaaaa ttttttagat gtagtatcta 99300 aaactacgtt cgatgaattc ctatctatag tcgtagatca cgttaaatca tctacggatg 99360 gatgatatag atctttacac aaataattac aaaaccgata aatggaaatg gataagcgta 99420 tgaaatctct cgcaatgaca gctttcttcg gagagctaaa cacattagat attatggcat 99480 tgataatgtc tatatttaaa cgccatccaa acaataccat tttttcagtg gataaggatg 99540 gtcagtttat gattgatttc gaatacgata attataaggc ttctcaatat ttggatctga 99600 ccctcactcc gatatctgga gatgaatgca agactcacgc atcgagtata gccgaacaat 99660 tggcgtgtgt ggatattatt aaagaggata ttagcgaata tatcaaaact actccccgtc 99720 ttaaacgatt tataaaaaaa taccgcaata gatcagatac tcgcatcagt cgagatacag 99780 aaaagcttaa aatagctcta gctaaaggca tagattacga atatataaaa gacgcttgtt 99840 aataagtaaa tgaaaaaaaa ctagtcgttt ataataaaac acgatatgga tgccaacgta 99900 gtatcatctt ctactattgc gacgtatata gacgctttag cgaagaatgc ttcggaatta 99960 gaacagaggt ctaccgcata cgaaataaat aatgaattgg aactagtatt tattaagccg 100020 ccattaatta ctttgacaaa tgtagtgaat atctctacga ttcaggaatc gtttattcga 100080 tttaccgtta ctaataagga aggtgtcaaa attagaacta agattccatt atctaaggta 100140 catggtctag atgtaaaaaa tgtacagtta gtagatgcta tagataacat agtttgggaa 100200 aagaaatcat tagtgacgga aaatcgtctt cacaaagaat gcttgttgag actatcgaca 100260 gaggaacgtc atatattttt ggattacaag aaatatggat cctctatccg actagaatta 100320 gtcaatctta ttcaagcaaa aacaaaaaac tttacgatag actttaagct aaaatatttt 100380 ctaggatccg gtgcccaatc taaaagttct ttgttgcacg ctattaatca tccaaagtca 100440 aggcctaata catctctgga aatagaattc acacctagag acaatgaaaa agttccatat 100500 gatgaactaa taaaggaatt gacgactcta tcacgtcata tatttatggc ttctccagag 100560 aatgtaattc tttctccgcc tattaacgca cctataaaga cttttatgtt gcctaaacaa 100620 gatatagtag gtctggatct ggaaaatcta tatgccgtaa ctaagactga cggcattcct 100680 ataactatca gagttacatc aaacgggttg tattgttatt ttacacatct tgggtatatt 100740 attagatatc cagttaagag aataatagat tccgaagtag tagtctttgg tgaggcagtt 100800 aaggataaga actggaccgt atatctcatt aagctaatag agcctgtgaa tgcaatcaat 100860 gatagactag aagaaagtaa gtatgttgaa tctaaactag tggatatttg tgatcggata 100920 gtattcaagt caaagaaata tgaaggtccg tttactacaa ctagtgaagt cgtcgatatg 100980 ttatctacat atttaccaaa gcaaccagaa ggtgttattc tgttctattc aaagggacct 101040 aaatctaaca ttgattttaa aattaaaaag gaaaatacta tagaccaaac tgcaaatgta 101100 gtatttaggt acatgtccag tgaaccaatt atctttggag aatcgtctat ctttgtagag 101160 tataagaaat ttagcaacga taaaggcttt cctaaagaat atggttctgg taagattgtg 101220 ttatataacg gcgttaatta tctaaataat atctattgtt tggaatatat taatacacat 101280 aatgaagtgg gtattaagtc cgtggttgta cctattaagt ttatagcaga attcttagtt 101340 aatggagaaa tacttaaacc tagaatcgat aaaaccatga aatatattaa ctcagaagat 101400 tattatgggaa atcaacataa tatcatagtc gaacatttaa gagatcaaag catcaaaata 101460 ggagatatct ttaacgagga taaactatcg gatgtggggac atcaatacgc caataatgat 101520 aaatttagat taaatccaga agttagttat tttacgaata aacgaactag aggaccgttg 101580 ggaattttat caaactacgt caagactctt cttatttcta tgtattgttc caaaacattt 101640 ttagacgatt ccaacaaacg aaaggtattg gcgattgatt ttggaaacgg tgctgacctg 101700 gaaaaatact tttatggaga gattgcgtta ttggtagcga cggatccgga tgctgatgct 101760 atagctagag gaaatgaaag atacaacaaa ttaaactctg gaattaaaac caagtactac 101820 aaatttgact acattcagga aactattcga tccgatacat ttgtctctag tgtcagagaa 101880 gtattctatt ttggaaagtt taatatcatc gactggcagt ttgctatcca ttattctttt 101940 catccgagac attatgctac cgtcatgaat aacttatccg aactaactgc ttctggaggc 102000 aaggtattaa tcactaccat ggacggagac aaattatcaa aattaacaga taaaaagact 102060 tttataattc ataagaattt acctagtagc gaaaactata tgtctgtaga aaaaatagct 102120 gatgatagaa tagtggtata taatccatca acaatgtcta ctccaatgac tgaatacatt 102180 atcaaaaaga acgatatagt cagagtgttt aacgaatacg gatttgttct tgtagataac 102240 gttgatttcg ctacaattat agaacgaagt aaaaagttta ttaatggcgc atctacaatg 102300 gaagatagac cgtctacaaa aaactttttc gaactaaata gaggagccat taaatgtgaa 102360 ggtttagatg tcgaagactt acttagttac tatgttgttt atgtcttttc taagcggtaa 102420 ataataatat ggtatgggtt ctgatatccc cgttctaaat gcattaaata attccaatag 102480 agcgattttt gttcctatag gaccttccaa ctgtggatac tctgtattgt taatagatat 102540 attaatactt ttgtcgggta acagaggttc tacgtcttct aaaaataaaa gtttgataac 102600 atctggcctg ttcataaata aaaacttggc gattctatat atactcttat tatcaaatct 102660 agccattgtc ttatagatgt gagctactgt aggtgtacca tttgattttc tttctaatac 102720 tatatatttc tctcgaagaa gttcttgcac atcatctggg aataaaatac tactgttgag 102780 taaatcagtt atttttttta tatcgatatt gatggacatt tttatagtta aggataataa 102840 gtatcccaaa gtcgataacg acgataacga agtatttata cttttaggaa atcacaatga 102900 ctttatcaga tcaaaattaa caaaattaaa ggagcatgta tttttttctg aatatattgt 102960 gactccagat acatatggat ctttatgcgt cgaattaaat gggtctagtt ttcagcacgg 103020 tggtagatat atagaggtgg aggaatttat agatgctgga agacaagtta gatggtgttc 103080 tacatccaat catatatctg aagatatacc cgaagatata cacactgata aatttgtcat 103140 ttatgatata tacacttttg acgctttcaa gaataaacga ttggtattcg tacaggtacc 103200 tccgtcgtta ggagatgata gctatttgac taatccgtta ttgtctccgt attatcgtaa 103260 ttcagtagcc agacaaatgg tcaatgatat gatttttaat caagattcat ttttaaaata 103320 tttattagaa catctgatta gaagccacta tagagtttct aaacatataaa caatagttag 103380 atacaaggat accgaagaat taaatctaac gagaatatgt tataatagag ataagtttaa 103440 ggcgtttgta ttcgcttggt ttaacggcgt ttcggaaaat gaaaaggtac tagatacgta 103500 taaaaaggta tctaatttga tataatgaat tcagtgactg tatcacacgc gccatatact 103560 attacttatc acgatgattg ggaaccagta atgagtcaat tggtagagtt ttataacgaa 103620 gtagccagtt ggctgctacg agacgagacg tcgcctattc ctgataagtt ctttatacag 103680 ttgaaacaac cgcttagaaa taaacgagta tgtgtgtgcg gtatagatcc gtatccgaaa 103740 gatggaactg gtgtaccgtt cgaatcacca aattttacaa aaaaatcaat taaggagata 103800 gcttcatcta tatctagatt aaccggagta attgattata aaggttataa ccttaatata 103860 atagacgggg ttataccctg gaattattac ttaagttgta aattaggaga aacaaaaagt 103920 cacgcgatct actgggataa gatttccaag ttactgctgc agcatataac taaacacgtt 103980 agtgttcttt attgtttggg taaaacagat ttctcgaata tacgggcaaa gttagaatcc 104040 ccggtaacta ccatagtggg atatcatcca gcggctagag accgtcaatt cgagaaagat 104100 cgatcatttg aaattatcaa cgttttactg gaattagaca acaaggtacc tataaattgg 104160 gctcaagggt ttatttatta atgctttagt gaaattttaa cttgtgttct aaatggatgc 104220 ggctattaga ggtaatgatg ttatctttgt tcttaagact ataggtgtcc cgtcagcgtg 104280 cagacaaaat gaagatccaa gatttgtaga agcatttaaa tgcgacgagt tagaaagata 104340 tattgagaat aatccagaat gtacactatt cgaaagtctt agggatgagg aagcatactc 104400 tatagtcaga attttcatgg atgtagattt agacgcgtgt ctagacgaaa tagattattt 104460 aacggctatt caagatttta ttatcgaggt gtcaaactgt gtagctagat tcgcgtttac 104520 agaatgcggc gccattcatg aaaatgtaat aaaatccatg agatctaatt tttcattgac 104580 taagtctaca aatagagata aaacaagttt tcatattatc tttttagaca cgtataccac 104640 tatggataca ttgatagcta tgaaacgaac actattagaa ttaagtagat catctgaaaa 104700 tccactaaca agatcgatag acactgccgt atataggaga aaaacaactc ttcgggttgt 104760 aggtactagg aaaaatccaa attgcgacac tattcatgta atgcaaccac ctcatgataa 104820 tatagaagat tacctattca cttacgtgga tatgaacaac aatagttatt acttttctct 104880 acaacgacga ttggaggatt tagttcctga taagttatgg gaaccagggt ttatttcatt 104940 cgaagacgct ataaaaagag tttcaaaaat attcattaat tctataataa actttaatga 105000 tctcgatgaa aataatttta caacggtacc actggtcata gattacgtaa caccttgtgc 105060 attatgtaaa aaacgatcgc ataaacatcc gcatcaacta tcgttggaaa atggtgctat 105120 tagaatttac aaaactggta atccacatag ttgtaaagtt aaaattgttc cgttggatgg 105180 taataaactg tttaatattg cacaaagaat tttagacact aactctgttt tattaaccga 105240 acgaggagac catatagttt ggattaataa ttcatggaaa tttaacagcg aagaaccctt 105300 gataacaaaa ctaattttgt caataagaca tcaactacct aaggaatatt caagcgaatt 105360 actctgtcca agaaaacgaa agactgtaga agctaacata cgagacatgt tagtagattc 105420 agtggagacc gatacctatc cggataaact tccgtttaaa aatggtgtat tggacctggt 105480 agacggaatg ttttactctg gagatgatgc taaaaaatat atgtgtactg tatcaaccgg 105540 atttaaattt gacgatacaa agttcgtcga agacagtcca gaaatggaag agttaatgaa 105600 tatcattaac gatatccaac cattaacgga tgaaaataag aaaaatagag agctatatga 105660 aaaaacatta tctagttgtt tatgcggtgc taccaaagga tgtttaacat tcttttttgg 105720 agaaactgca actggaaagt cgacaaccaa acgtttgtta aagtctgcta tcggtgacct 105780 gtttgttgag acgggtcaaa caattttaac agatgtattg gataaaggac ctaatccatt 105840 tatcgctaac atgcatttga aaagatctgt attctgtagc gaactacctg attttgcatg 105900 tagtgggtca aagaaaatca gatctgataa tattaaaaag ttgacagaac cttgtgtcat 105960 tggaagaccg tgtttctcca ataaaattaa taatagaaac catgcgacaa tcattatcga 106020 tactaattac aaacctgttt ttgataggat agataacgca ttaatgagaa gaattgccgt 106080 cgtgcgattc agaacacact tttctcaacc ttctggtaga gaggctgctg aaaataatga 106140 cgcgtacgat aaagtcaaac tattagacga ggggttagat ggtaaaatac aaaataatag 106200 atatagattc gcatttctat acttgttggt gaaatggtac agaaaatatc atgttcctat 106260 tatgaaacta tatcctacac ccgaagagat tcctgacttt gcattctatc tcaaaatagg 106320 tactctgttg gtatctagct ctgtaaagca tattccatta atgacggacc tctccaaaaa 106380 gggatatata ttgtacgata atgtggtcac tcttccgttg actactttcc aacagaaaat 106440 atccaagtat tttaattcta gactatttgg acacgatata gagagcttca tcaatagaca 106500 taagaaattt gccaatgtta gtgatgaata tctgcaatat atattcatag aggatatttc 106560 atctccgtaa atatatgctc atatatttat agaagatatc acatatctaa atgaataccg 106620 gaattataga tttattgat aatcatgttg atagtatacc aactatatta cctcatcagt 106680 tagctactct agattatcta gttagaacta tcatagatga gaacagaagc gtgtattgt 106740 tccatattat gggatcaggt aaaacaataa tcgctttgtt gttcgccttg gtagcttcca 106800 gatttaaaaa ggtttacatt ctagtgccga acatcaacat cttaaaaatt ttcaattata 106860 atatgggtgt agctatgaac ttgtttaatg acgaattcat agctgagaat atctttattc 106920 attccacaac aagtttttat tctcttaatt ataacgataa cgtcattaat tataacggat 106980 tatctcgcta caataactct atttttatcg ttgatgaggc acataatatc tttgggaata 107040 atactggaga acttatgacc gtgataaaaa ataaaaacaa gattcctttt ctactattgt 107100 ctggatctcc cattactaac acacctaata ctctgggtca tattatagat ttaatgtccg 107160 aagagacgat agattttggt gaaattatta gtcgtggtaa gaaagtaatt cagacacttc 107220 ttaacgaacg cggtgtgaat gtacttaagg atttgcttaa aggaagaata tcatattacg 107280 aaatgcctga taaagatcta ccaacgataa gatatcacgg acgtaagttt ctagatacta 107340 gagtagtata ttgtcacatg tctaaacttc aagagagaga ttatatgatt actagacgac 107400 agctatgtta tcatgaaatg tttgataaaa atatgtataa cgtgtcaatg gcagtattgg 107460 gacaacttaa tctgatgaat aatttagata ctttatttca ggaacaggat aaggaattgt 107520 acccaaatct gaaaataaat aatggcgtgt tatacggaga agaattggta acgttaaaca 107580 ttagttccaa atttaaatac tttattaatc ggatacagac actcaacgga aaacatttta 107640 tatacttttc taattctaca tatggcggat tggtaattaa atatatcatg ctcagtaatg 107700 gatattctga atataatggt tctcagggaa ctaatccaca tatgataaac ggcaaaccaa 107760 aaacatttgc tatcgttact agtaaaatga aatcgtcttt agaggatcta ttagatgtgt 107820 ataattctcc tgaaaacgat gatggcagtc aattgatgtt tttgttttcg tcaaacatta 107880 tgtccgaatc ctatactctg aaagaggtaa ggcatatttg gtttatgact atcccagata 107940 cttttctca atacaaccaa attcttggac gatctattag aaaattctct tacgccgata 108000 tttctgaacc agttaatgta tatcttttag ccgccgtata ttccgatttc aatgacgaag 108060 tgacgtcatt aaacgattac acacaggatg aattaattaa tgttttacca tttgacatca 108120 aaaagctgtt gtatctaaaa tttaagacta aagaaacgaa tagaatatac tctattcttc 108180 aagagatgtc tgaaacgtat tctcttccac cacatccatc aattgtaaaa gttttattgg 108240 gagaattggt cagacaattt ttttataata attctcgtat taagtataac gataccaagt 108300 tacttaaaat ggttacatca gttataaaaa ataaagaaga cgctaggaat tacatagatg 108360 atattgtaaa cggtcacttc tttgtatcga ataaagtatt tgataaatct cttttataca 108420 aatacgaaaa cgatattatt acagtaccgt ttagactttc ctacgaacca tttgtttggg 108480 gagttaactt tcgtaaagaa tataacgtgg tatcttctcc ataaaactga tgagatatat 108540 aaagaaataa atgtcgagct ttgttaccaa tggatacctt ccagttacat tggagccaca 108600 cgagctgacg ttagacataa aaactaatat taggaatgcc gtatataaga cgtatctcca 108660 tagagaaatt agtggtaaaa tggccaagaa aatagaaatt cgtgaagacg tggaattacc 108720 tctcggcgaa atagttaata attctgtagt tataaacgtt ccgtgtgtaa taacctacgc 108780 gtattatcac gttggggata tagtcagagg aacattaaac atcgaagatg aatcaaatgt 108840 aactattcaa tgtggagatt taatctgtaa actaagtaga gattcgggta ctgtatcatt 108900 tagcgattca aagtactgct tttttcgaaa tggtaatgcg tatgacaatg gcagcgaagt 108960 cactgccgtt ctaatggagg ctcaacaagg tatcgaatct agttttgttt ttctcgcgaa 109020 tatcgttgac tcataaaaaa gagaatagcg gtaagtataa acacgaatac tatggcaata 109080 attgcgaatg tttattccc ttcgatatat ttttgataat atgaaaaaca tgtctctctc 109140 aaatcggaca accatctcat aaaatagttc tcgcgcgctg gagaggtagt tgctgctcgt 109200 ataatctccc cagaataata tacttgcgtg tcgtcgttca atttatacgg atttctatag 109260 ttctctgtta tataatgcgg ttttccatca tgattagacg acgacaatag tgttctaaat 109320 ttagatagtt gatcagaatg aatgtttatt ggcgttggaa aaattatcca tacagcgtct 109380 gcagagtggt tgatagttgt tcctagatat gtaaaataat ccaacttact aggcagcaaa 109440 ttgtctagat aaaatactga atcaaacggt gcagacgtat tggtggatct aatggaatcc 109500 aattgattaa ctatcttttg aaaatataca tttttatgat ccgatacttg taagaatata 109560 gaaataatga taagtccatc atcgtgtttt tttgcctctt cataagaact atattttttc 109620 ttattccaat gaacaagatt aatctctcca gagtatttgt acacatctat caagtgattg 109680 gatccataat cgtcttcctt tccccaatat atacgtagtg atgataacac atattcattg 109740 gggagaaacc ctccacttat atatcctcct ttaaaattaa tccttactag ttttccagtg 109800 ttctggatag tggttggttt cgactcatta taatgtatgt ctaacggctt caatcgcgcg 109860 ttagaaattg cttttttagt ttctatatta ataggagata gttgttgcgg catagtaaaa 109920 atgaaatgat aactgtttaa aaatagctct tagtatggga attacaatgg atgaggaagt 109980 gatatttgaa actcctagag aattaatatc tattaaacga ataaaagata ttccaagatc 110040 aaaagacacg catgtgtttg ctgcgtgtat aacaagtgac ggatatccgt taataggagc 110100 tagaagaact tcattcgcat tccaagcgat attatctcaa caaaattcag attctatctt 110160 tagagtatcc actaaactat tacggtttat gtactacaat gaactaagag aaatctttag 110220 acggttgaga aaaggttcta tcaacgatat cgatcctcac tttgaagagt taatattatt 110280 gggtggtaaa ctagataaaa aggaatctat taaagattgt ttaagaagag aattaaaaga 110340 ggaaagtgat gaacgtataa cagtaaaaga atttggaaat gtaattctaa aacttacaac 110400 acgggataaa ttatttaata aagtatatat aagttattgc atggcgtgtt ttattaatca 110460 atcgttggag gatttatcgc atactagtat ttacaatgta gaaattagaa agattaaatc 110520 attaaatgat tgtattaacg acgataaata cgaatatctg tctttatattt ataatatgct 110580 agttaatagt aaatgaactt ttacagatct agtataatta gtcagattat taagtataat 110640 agacgactag ctaagtctat tatttgcgag gatgactctc aaattattac actcacggca 110700 ttcgttaacc aatgcctatg gtgtcataaa cgagtatccg tgtccgctat tttattaact 110760 actgataaca aaatattagt atgtaacaga cgagatagtt ttctctattc tgaaataatt 110820 agaactagaa acatgtctag aaagaaacga ttattctga attattccaa ttatttgtcc 110880 aaacaggaaa gaagtatact atcgtcattt ttttctctag atccagctac tactgataat 110940 gatagaatag atgctattta tccgggtggc atacccaaaa ggggtgagaa tgttccagag 111000 tgtttatcca gggaaattaa agaagaagtt aatatagaca attcttttgt attcatagac 111060 actcggtttt ttattcatgg catcatagaa gataccatta ttaataaatt ttttgaggta 111120 atcttctttg tcggaagaat atctttaacg agtgatcaaa tcattgatac atttaaaagt 111180 aatcatgaaa tcaaggatct aatattttta gatccgaatt caggtaatgg actccaatac 111240 gaaattgcaa aatatgctct agatactgca aaactcaaat gttatggcca tagaggatgt 111300 tattacgaat cattaaaaaa attaactgag gatgattgat tagaaaatat aaattaattt 111360 accatcgtgt atttttataa cgggattgtc cggcatatca tgtagatagt taccgtctac 111420 atcgtatact cgaccatcta cgcctttaaa tcctctattt attgacatta atctattaga 111480 attggaatac caaatattag taccctcaat tagttattg gtaatatttt ttttagacga 111540 tagatcgatg gctcttgaaa ccaaggtttt ccaaccggac tcattgtcga tcggtgagaa 111600 gtctttttca ttagcatgaa tccattctaa tgatgtatgt ttaaacactc taaacaattg 111660 gacaaattct tttgatttgc tttgaatgat ttcaaatagg tcttcgtcta cagtaggcat 111720 accattagat aatctagcca ttataaagtg cacgtttaca tatctacgtt ctggaggagt 111780 aagaacgtga ctattgagac gaatggctct tcctactatc tgacgaagag acgcctcgtt 111840 ccatgtcata tctaaaatga agatatcatt aattgagaaa aaactaatac cctcgcctcc 111900 actagaagag aatacgcatg ttttaatgca ttctccgtta gtgtttgatt cttggttaaa 111960 ctcagccacc gccttgattc tagtatcttt tgttctagat gagaactcta tattagagat 112020 accaaagact ttgaaatata gtaataagat ttctattcct gactgattaa caaatggttc 112080 aaagactaga catttaccat gggatgctaa tattcccaaa catacatcta taaatttgac 112140 gcttttctct tttaattcag taaatagaga gatatcagcc gcactagcat cccctttcaa 112200 tagttctccc tttttaaagg tatctaatgc ggatttagaa aactctctat ctcttaatga 112260 atttttaaaa tcattatata gtgttgctat ctcttgcgcg tattcgcccg gatcacgatt 112320 ttgtctttca ggaaagctat cgaacgtaaa cgtagtagcc atacgtctca gaattctaaa 112380 tgatgatata cctgttttta tttcagcgag tttagccttt tgataaattt cttcttgctt 112440 tttcgacata ttaacgtatc gcattaatac tgttttctta gcgaatgatg cagacccttc 112500 tacgtcatca aaaatagaaa actcgttatt aactatgtac gaacataggc ctcctagttt 112560 ggagactaat tctttctcat caactagacg tttatctca aatagcgatt ggtgttgtaa 112620 ggatcctggt cgtagtaagt taaccaacat ggtgaattct tgcacactat taacgatagg 112680 tgtagccgat aaacaaatca tcttatggtt ttttaatgcg atggtcttag ataaaaaatt 112740 atatactgaa cgagtaggac ggatcttacc atcttctttg attaatgatt tagaaatgaa 112800 gttatgacat tcatcaataa tgacgcatat tctactcttg gaattaatag ttttgatatt 112860 agtaaaaaat ttatttctaa aattttgatc atcgtaatta ataaaaatac aatccttcgt 112920 tatctctgga gcgtatctga gtatagtgtt catccaagga tcttctatca aagccttttt 112980 caccaataag ataatagccc aattcgtata aatatcctta agatgtttga gaatatatac 113040 agtagtcatt gttttaccaa cacccgtttc atggaacaat aaaagagaat gcatactgtc 113100 taatcctaag aaaactcttg ctacaaaatg ttgataatcc ttgaggcgta ctacgtctgt 113160 tcccatcatt tcaacaggca tattagtagt tctgcgcaat gcataatcga tataggccgc 113220 gtgtgattta ctcatttatg agtgataagt aataactatg ttttaaaaat cacagcagta 113280 gtttaactag tcttctctga tgtttgtttt cgatactttt tgaatcagaa gtcatactag 113340 aataaagcaa cgagtgaacg taatagagag cttcgtatac tctattcgaa aactctaaga 113400 acttattaat gaattccgta tccactggat tgtttaaaat actaaattga acactgttca 113460 catccttcca agaagaagac ttagtgacgg acttaacatg agacataaat aaatccaaat 113520 tttttttaca aacatcacta gccaccataa tggcgctatc tttcaaccag ctatcgctta 113580 cgcattttag cagtctaaca tttttaaaga gactacaata tattctcata gtatcgatta 113640 cacctctacc gaataaagtt ggaagtttaa taatacaata tttttcgttt acaaaatcaa 113700 ataatggtcg aaacacgtcg aaggttaaca tcttataatc gctaatgtat agattgtttt 113760 cagtgagatg attattagat ttaatagcat ctcgttcacg tttgaacagt ttatgtgtgg 113820 cgctgaggtc ggcaactacg gcgtccgctt tagtactcct cccataatac tttacgctat 113880 taatctttaa aatttcatag actttatcta gatcgctttc tggtaacatg atatcatgtg 113940 taaaaagttt taacatgtcg gtcggcattc tatttagatc attaactcta gaaatctgaa 114000 gaaagtaatt agctccgtat tccagactag gtaatgggct tttacctaaa gacaagttaa 114060 gttctggcaa tgtttcataa aatggaagaa ggacatgcgt tccctcccgg atatttttta 114120 caatttcatc catttacaac tctatagttt gttttcatta ttattagtta ttatctccca 114180 taatcttggt aatacttacc ccttgatcgt aagatacctt atacaggtca ttacatacaa 114240 ctaccaattg tttttgtaca taatagattg gatggttgac atccatggtg gaataaacta 114300 ctcgaacaga tagtttatct ttcccccctag atacattggc cgtaatagtt gtcggcctaa 114360 agaatatctt tggtgtaaag ttaaaagtta gggttcttgt tccattattg ctttttgtca 114420 gtagttcatt ataaattctc gagatgggtc cgttctctga atatagaaca tcatttccaa 114480 atctaacttc tagtctagaa ataatatcgg tcttattctt aaaatctatt cccttgatga 114540 agggatcgtt aatgaacaaa tccttggcct ttgattcggc tgatctatta tctccgttat 114600 agacgttacg ttgactagtc caaagactta caggaataga tgtatcgatg atgttgatac 114660 tatgtgatat gtgagcaaag attgttctct tagtggcatc actatatgtt ccagtaatgg 114720 cggaaaactt tttagaaatg ttatatataa aagaattttt tcgtgttcca aacattagca 114780 gattagtatg aagataaaca ctcatattat caggaacatt atcaattttt acatacacat 114840 cagcatcttg aatagaaacg ataccatctt ctggaacctc aacaatctcg gcagactccg 114900 gataaccagt cggtgggcca tcactaacaa taactagatc atccaacaat ctactcacat 114960 atgcatctat ataatctttt tcatcttggg agtaccctgg atacgaaata aatttattat 115020 ccgtatttcc ataataaggt ttagtataaa cagagagcga tgttgccgca tgaacttcag 115080 ttacagtcgc cgttggttgg tttattgac ctattactct cctaggtttc tctataaacg 115140 atggtttaat ttgtacattc ttaaccatat atccaataaa gctcaattca ggaacataaa 115200 caaattcttt gttgaacgtt tcaaagtcga acgaagagtc acgaataacg atatcggata 115260 ctggattgaa ggttaccgtt acggtaattt ttgaatcgga tagtttaaga ctgctgaatg 115320 tatcttccac atcaaacgga gttttaatat aaacgtatac tgtagatggt tctttaatag 115380 tgtcattagg agttaggcca atagaaatat cattaagttc actagaatat ccagagtgtt 115440 tcaaagcaat tgtattattg atacaattat tatataattc ttcgccctca atttcccaaa 115500 taacaccgtt acacgaagag atagatacgt gattaataca tttatacca acatatggta 115560 cgtaaccgaa tcttcccata cctttaactt ctggaagttc caaactcaga accaaatgat 115620 taagcgcagt aatatactga tccctaattt cgaagctagc gatagcctga ttgtctggac 115680 catcgtttgt cataactccg gatagagaaa tatattgcgg catatataaa gttggaattt 115740 gactatcgac tgcgaagaca ttagaccgtt taatagagtc atccccaccg atcaaagaat 115800 taatgatagt attattcatt ttctatttaa aatggaaaaa gcttacaata aactccgtag 115860 agaaatatct ataatttgtg agttttcctt aaagtaacag cttccgtaaa cgccgtcttt 115920 atctcttagt aagttattg tatttataac cttttcctta tcttcataga atactaaagg 115980 caacaaagaa atttttggtt cttctctaag agctacgtga gacttaacca tagaagccaa 116040 cgaatcccta catattttag aacagaaata ccctacttca ccacccttgt atgtctcaat 116100 actaataggt ctaaaaacca aatcttgatt acaaaaccaa cacttatcaa ttacactatt 116160 tgtcttaata gacacatctg ccatagattt ataatacttt ggtagtatac aagcgagtgc 116220 ttcttcttta gcgggcttaa agactgcttt aggtgctgaa ataaccacat ctggaaggct 116280 tactcgctta gccatttaat tacggaacta tttttttata cttctaatga gcaagtagaa 116340 aacctctcat ctacaaaaac atactcgtgt ccataatcct ctaccatagt tacacgtttt 116400 ttagatctca tatgtgctaa aaagttttcc catactaatt ggttactatt atttttcgta 116460 taatttttaa cagtttgagg ttttagattt ttagttacag aagtgatatc gaatatttta 116520 tccaaaaaga atgaataatt aattgtctta gaaggagtgt tttcttggca aaagaatacc 116580 aagtgcttaa atatttctac tacttcatta atcttttctg tactcagatt cagtttctca 116640 tcttttactt gattgattat ttcaaagact aacttataat cctttttat tattctctcg 116700 ttagccttaa gaaaactaga tacaaaattt gcatctacat catccgtgga tatttgattt 116760 ttttccatga tatccaagag ttccgagata atttctccag aacattgatg agacaataat 116820 ctccgcaata catttctcaa atgaataagt ttattagaca cgtggaagtt tgactttttt 116880 tgtacctttg tacatttttg aaataccgac tcgcaaaaaa tacaatattc atatccttgt 116940 tcagatacta taccgttgtg tctacaaccg ctacataatc gtagattcat gttaacactc 117000 tacgtatctc gtcgtccaat attttatata aaaacatttt atttctagac gttgccagaa 117060 aatcctgtaa tacttttagt tttttgggct gtgaataaag tatcgcccta atatggttac 117120 cgtcctccgc caatatagta gttaaattat ccgcacatgc aaaagaacac cgcttaggcg 117180 gattcagtac aatgttatat ttttcgtacc aactcattta aatatcataa tctaaaatag 117240 ttctgtaata tgtctagcgc taatatattg atcataatcc tgtgcataaa ttaagataca 117300 acaatgtctc gaaatcatcg acatggcttc ttccatagtt agaagatcgt cgtcaaagtt 117360 agcaacgtga ttcatcaaca tttgctgttt tgaggcagca aatactgaac cgtcgccatt 117420 caaccattca taaaaaccat cgtctgaatc cattgataat ttcttgtact ggtttttgag 117480 agctcgcatc aatctagcat ttctagctcc cggattgaaa acagaaagag gatcgtacat 117540 ccagggtcca ttttctgtaa atagaatcgt ataatgtccc ttcaagaaga tatcagacga 117600 tccacaatca aagaattggt ctccgagttt gtaacaaaca gcggacttta acctatacat 117660 gataccgttt agcatgattt ctggtgatac gtcaatcgga gtatcatcta ttagagatct 117720 aaagccggtg taacattctc caccaaacat attcttattc tgacgtcgtt ctacataaaa 117780 catcattgct ccattaacga taacagggga atgaacagca ctacccatca cattagttcc 117840 caatggatca atgtgtgtaa ctccagaaca tcttccatat cctatgttag gaggagcgaa 117900 caccactctt ccactattgc catcgaatgc catagaataa atatccttgg aattgataga 117960 aatcggactg tcggatgttg tgatcatctt cataggatta acaactatgt atggtgccgc 118020 ctgaagtttc atatcgtaac tgatgccgtt tataggtcta gccacagaaa ccaacgtagg 118080 tctaaatcca actatagaca aaatagaagc caatatctgt tcctcatctg tcataacttg 118140 agagcatcca gtatgaataa tcttcattag atggggatct accgcatcat catcgttaca 118200 ataaaaaatt cccattctaa tgttcataat tgcttttcta atcatggtat gcatgtttgc 118260 tctctgaatc tctgtgggaaa ttagatctga tacacctgta atcactatcg gattatcctc 118320 cgtaagacga ttaaccaaca acatataatt ataagacttt acttttctaa attcataaag 118380 ttgctggatt aggctatagg tgtctccatg tacatacgcg ttctcgagcg caggaagttt 118440 aataccgaat agtgccatca gaataggatg aatatagtaa ttagtttctg gttttctata 118500 aataaaagac aaatcttgtg aactagacat atcggtaaaa tgcatggatt ggaatcgtgt 118560 agtcgacaga agaatatgat gattagatgg agagtatatt ttatctaact ctttgagttg 118620 gtcaccgatt ctaggactag ctcgagaatg aataagtact aaaggatgag tacatttcac 118680 agaaacacta gcattgttca atgtgctctt tacatgggta aggagttgaa atagctcgtt 118740 tctatttgtt ctgacaatat ttagtttatt cataatgtta agcatatcct gaatagtaaa 118800 gttagatgtg tcatacttgt tagtagttag atatttagca attgcattcc catcatttct 118860 caatctcgta ctccaatcat gtgtagatgc tacttcatct atagaaacca tacaatcctt 118920 tttgataggc tgttgagatt gattatttcc tgcacgttta ggtttggtac gttgatttct 118980 agcccctgcg gatataaagt catcgtctac aatttgggac aatgaattgc atacactaca 119040 agacaaagat ttatcagaag tgtgaatatg atcttcatct accaaagaaa gagtttgatt 119100 agtataacta gattttagtc ctgcgttaga tgttaaaaaa acatcgctat tgaccacggc 119160 ttccattatt tatattcgta gtttttactc gaaagcgtga ttttaatatc caatcttatt 119220 acttttggaa tcgttcaaaa cctttgacta attgtagaat ttgatctatt gccctacgcg 119280 tatactccct tgcatcatat acgttcgtca ccagatcgtt tgtttcggcc tgaagttggt 119340 gcatatctct ttcaacattc gacatgagat ccttaagggc catatcgtct agattttgtt 119400 gagatgctgc tcctggattt ggattttgtt gtgctgttgt acatactgta ccaccagtag 119460 gtgtaggagt acatacagtg gccacaatag gaggttgaga aagtgtaacc gttggagtag 119520 tacaagaaat atttccatcc gattgttgtg tacatgtagt tgttggtaac gtctgagaag 119580 gttgggtaga tggcggtgtc gtcgtctttt gatctttat aaatttagag ataatatcct 119640 gaacagcatt gctcggcgtc aacgctggaa ggaggtgaact cgccggcgca tcagtatctt 119700 cagacagcca atcaaaaaga ttagacatat cagatgatgt attagtttgt tgtcgtggtt 119760 ttggtgtagg agcagtacta ctaggtagaa gaataggagc cggtgtagct gttggaaccg 119820 gctgtggagt tatatgaata gttggttgta gcggttggat aggctgtctg ctggcggcca 119880 tcatattatc tctagctagt tgttctcgca actgtctttg ataatacgac tcttgagact 119940 ttagtcctat ttcaatcgct tcatcctttt tcgtatccgg atccttttct tcagaataat 120000 agattgacga ctttggtgta gaggattctg ccagcccctg tgagaacttg ttaaagaagt 120060 ccatttaagg ctttaaaatt gaattgcgat tataagatta aatggcagac acagacgata 120120 ttatcgacta tgaatccgat gatctcaccg aatacgagga tgatgaagaa gaggaagaag 120180 atggagagtc actagaaact agtgatatag atcccaaatc ttcttataag attgtagaat 120240 cagcatccac tcatatagaa gatgcgcatt ccaatcttaa acatataggg aatcatatat 120300 ctgctcttaa acgacgctat actagacgta taagtctatt tgaaatagcg ggtataatag 120360 cagaaagcta taacttgctt caacgaggaa gattacctct agtttcagaa ttttctgacg 120420 aaacgatgaa gcaaaatatg ctacatgtaa ttatacaaga gatagaggag ggttcttgtc 120480 ctatagtcat cgaaaagaac ggagaattgt tgtcggtaaa cgattttgac aaagatggtc 120540 taaaattcca tctagactat attatcaaaa tttggaaact tcaaaaacga tattagaatt 120600 tatacgaata tcgttctcta aatgtcacaa tcaagtctcg catgttcagc aatttattgt 120660 cgtactttat atcgtgttca ttaacgatat cttgcaaaat agtaatgatt ctatcttcct 120720 tcgatagata ttcttcagag attattgtct tatattcttt cttgttatca gatatgaatt 120780 tgataagact ttgaacatta ttgatacccg tctgtttaat tttttctaca gatattttag 120840 ttttggcaga ttctatcgta tctgtcaata gacatccaac atcgacattc gacgtcaatt 120900 gtctataaat caacgtataa attttagaaa taacattagc gaattgttgt gcattgatgt 120960 cgttatctg aaacagtatg attttaggta gcattttctt aacaaagaga acgtatttat 121020 tgttactcag ttgaacagat gatatatcca gattactaac gcatctgatt ccatatacca 121080 aactttcaga agaaatggtg tacaattgtt tgtattcatt caatgtctct ttttcagaaa 121140 ttagtttaga gtcgaatact gcaataattt tcaagagata gttttcatca gataagattt 121200 tatttagtgt agatatgata aaactattgt tttgttggag aacttgatac gccgcgttct 121260 ctgtagtcga cgctctcaaa tgggaaacaa tctccattat ttttttggaa tcggatacta 121320 tatcttcggt atcttgacgc agtctagtat acatagagtt aagagagatt agagtttgta 121380 cattaagcaa catgtctcta aatgtggcta caaacttttc ctttttcaca tcatctagtt 121440 tattatatac cgatttcaca acggcaccag atttaaggaa ccagaatgaa aaactctgat 121500 aactacaata tttcatcata gttacgattt tatcatcttc tatagttggt gtaatagcgc 121560 ataccttttt ctccaagact ggaaccaacg tcataaaaat gtttaaatca aaatccatat 121620 caacatctga tgcgctaaga ccagtctcgc gttcaagatt atctttaacta atggtgacga 121680 actcatcgta taaaactcta agtttgtcca ttattatattt acagatttag ttgtttaatt 121740 tatttgtgct cttccagagt tgggatagta tttttctaac gtcggtatta tattattagg 121800 atctacgttc atatgtatca taatattaat catccacgtt ttgataaatc tatctttagc 121860 ttctgaaata acgtatttaa acaaaggaga aaaatattta gctacggcat cagacgcaat 121920 aacatttttt gtaaatgtaa cgtatttaga cgacagatct tcgttaaaaa gttttccatc 121980 tatgtagaat ccatcggttg ttaacaccat tcccgcgtca gattgaatag gagtttgaat 122040 agtttgtttt ggaaatagat ccttcaataa cttatagttg ggtgggaaaa aatcgatttt 122100 atcactagac tctttctttt ttactatcat tacctcatga actatttctt gaatgagtat 122160 atgtattttc tttcctatat cggacgcgtt cattggaaaa tataccatgt cgttaactat 122220 aagaatattt ttatcctcgt ttacaaactg aataatatca gatgtagttc gtaaacgaac 122280 tatatcatca ccagcacaac atctaactat atgatatcca ctagtttcct ttagccgttt 122340 attatcttgt tccatattag cagtcattcc atcatttaag aaggcgtcaa agataatagg 122400 gagaaatgac attttggatt ctgttacgac tttaccaaaa ttaaggatat acggacttac 122460 tatctttttc tcaacgtcga tttgatgaac acacgatgaa aatgtgcttc tatgagattg 122520 atcatgtaga aaacaacaag ggatacaata tttccgcata tcatgaaata tattaagaaa 122580 tcccacctta ttatatttcc ccaaaggatc catgcacgta aacattatgc cgttatcatt 122640 aataaagact tctttctcat cggatctgta aaagttgtta ctgatttttt tcattccagg 122700 atctagataa ttaataatga tgggttttct attcttattc tttgtatttt ggcatatcct 122760 agaccagtaa acagtttcca ctttggtaaa atcagcagac ttttgaacgc tattaaacat 122820 ggcattaatg gcaataacta aaaatgtaaa atatttttct atgttaggaa tatggttttt 122880 cactttaata gatatatggt ttttggccaa aatgatagat atttttttat ccgaggatag 122940 taaaatatta ttagtcgccg tctctataaa aatgaagcta gtctcgatat ccaattttat 123000 tctagaattg ataggagtcg ccaaatgtac cttatacgtt atatctccct tgatgcgttc 123060 catttgtgta tctatatcgg acacaagatc tgtaaatagt tttacgttat taatcatcac 123120 ggtatcgccg tcgctagata acgctaatgt accatccaag tcccaaatgg agagatttaa 123180 ctgttcatcg tttagaataa aatgattacc ggtcatatta ataaagtgtt catcgtatct 123240 agataacaac gacttataat taatgtccaa gtcttgaact cgctgaatga tcttttttaa 123300 cccagttagt tttagattgg tacgaaatat attgttaaac tttgattcta cagtaatgtc 123360 caaatctagt tgtggaaata cttccatcaa cattgtttca aacttgataa tattattatc 123420 tacatcttcg tacgatccaa attccggaat agatgtatcg cacgctctgg ccacccagat 123480 aaccaaaaag tcacacgctc caggatatac attgtataaa aagctatcgt tttttagtag 123540 ggtttttttc tgcgtgtata cgaagggatt aaaaatagta ttatcaacgt aactatattc 123600 caaattattc ttatgagaat agataataat atcgtcctta atatctaaca aatttcctaa 123660 atatcccttt aattgagtca ttcgaagcgt caatagaata tgtctcttaa ctatttccgg 123720 ctgttgtata tttaaatgac ttcgtaaaaa ataatatatg ggcgacttct catctatgta 123780 atcatatgga gtgagatata gggctcgttc tacctcctgc cccttaccca cctgtaatac 123840 caattgcgga cttactatat atcgcatatt tatatcgtgg ggtaaagtga aaatctacta 123900 ccgatgatgt aagtcttaca atgttcgaac cagtaccaga tcttaatttg gaggcctccg 123960 tagaactagg ggaggtaaat atagatcaaa caacacctat gataaaggag aatagcggtt 124020 ttatatcccg cagtagacgt ctattcgccc atagatctaa ggatgatgaa agaaaactag 124080 cactacgatt ctttttacaa agactttatt ttttagatca tagagagatt cattatttgt 124140 tcagatgcgt tgacgctgta aaagacgtca ctattaccaa aaaaataac attatcgtgg 124200 cgccttatat agcactttta actatcgcat caaaaggatg caaacttaca gaaacaatga 124260 ttgaagcatt ctttccagaa ctatataatg aacatagtaa gaaatttaaa ttcaactctc 124320 aagtatccat catccaagaa aaactcggat accagtttgg aaactatcac gtttatgatt 124380 ttgaaccgta ttactctaca gtagctctgg ctattcgaga tgaacattca tctggcattt 124440 ttaatatccg tcaagagagt tatctggtaa gttcattatc tgaaataaca tatagatttt 124500 atctaattaa tctaaaatct gatcttgttc aatggagtgc tagtacgggc gctgtaatta 124560 atcaaatggt aaatactgta ttgattacag tgtatgaaaa gttacaactg gtcatagaaa 124620 atgattcaca atttacatgt tcattggctg tggaatcaaa acttccaata aaattactta 124680 aagatagaaa tgaattattt acaaaattca ttaacgagtt aaaaaagacc agttcattca 124740 agataagcaa acgcgataag gatacgctac taaaatattt tacttaggac tggagttaga 124800 atttatagac gactcatttc gtttatcatt gttactatta ttactattac tatcattatt 124860 agtgttggca ttattagtat tcttcttgtc atcttgttca gaaatataca gcaatgctat 124920 acctaatact aaatacatta tcatgctcgc aatggctcta acaacaacga accaaaatga 124980 atttggtcgt agcttttgtt cacaaaaata cataaagaaa tgtctacata aatctatggc 125040 gccattggct acttgaaata gcgccagtcc tcctacagat tttaatatag ctgtataaca 125100 tgacatttat tcatcatcaa aagagacaga gtcaccatct gtcatattta gatttttttt 125160 catgtgttca aagtatcctc tactcatttc attataatag tttatcatac ttagaatttt 125220 aggacggatc aatgagtaag acttgactag atcgtcagta gtaatttgtg catcgtctat 125280 tctgcatccg cttcgtcgaa taatgtatag catcgctttg agattctcca tagctatcaa 125340 gtctttatac aatgacatgg aaatatctgt gaatacttta tacttctcca acatcgatgc 125400 cttaacatca tcgcctactt tagcattgaa aatacgttct attgtgtaga tggatgtagc 125460 aagattttta aacaacaatg ccatcttaca cgatgattgc ctcaagtctc caatcgtttg 125520 tttagaacga ttagctacag agtccaatgc ttggctgact agcatattat tatctttaga 125580 aattgtattc ttcaatgagg cgtttatcat atctgtgatt tcgttagtca tattacagtc 125640 tgactgggtt gtaatgttat ccaacatatc acctatggat acggtacacg taccagcatt 125700 tgtaataatc ctatctaaga tgttgtatgg cattgcgcag aaaatatctt ctcctgtaat 125760 atttccactc tcgataaatc tactcagatt attcttaaat gccttattct ctggagaaaa 125820 gatatcagtg tccatcattt cattaatagt atacgcagaa aagataccac gagtatcaat 125880 tctatccaag atacttatcg gttccgagtc acagataatg gtttcctctc cttcgggaga 125940 tcctgcatag aaatatctag gacaatagtt tctatactgt ctgtaactct gataatctct 126000 aaagtcacta actgatacca tgaaattgag aagatcaaac gctgaagtaa ttaatttttc 126060 tgcctcgttt ttactacaac tagttttcat caatgtagtg acgatgtatt gtttagttac 126120 ttttggtcta atactgatga tagagatatt attacttccc ataatggatc ttctagtagt 126180 caccttaaag cccattgatg caaatagcag atagataaag tcttggtatg actcctttct 126240 aatatagtac ggactacctt tgtcacccaa ctttataccc acataagcca taacaacctc 126300 tttaatagcc gtttcatgag gtttatcagc catgagcctg agtagttgga agaatctcat 126360 gaatcctgtc tcagaaagtc ctatatgcat gatagattta tctttcctgg gaaactctcg 126420 tatagtcata gatgaaatac tcttcaaagt ttctgaaata agattagtaa cagtcttacc 126480 tccgactact ctaggtaaca aacaaactct aataggtgtt ttctctgcgg agataatatc 126540 agaaaggata gagcaataag tagtattatt gtgattataa agaccgaata cataacaggt 126600 agaatttata aacatcatgt cctgaaggtt tttagacttg tattcctcgt aatccatacc 126660 gtcccaaaac atggatttgg taactttgat agccgtagat ctttgttcct tcgccaacag 126720 gttaaagaaa ttaataaaga atttgtggtt tctacctatg tctacaaatt gcacgtttgg 126780 aagcgccacg gttacattca ctgcagcatt ttgaggatcg cgagtatgaa gtacgatgtt 126840 attgtttact ggtatatctg gaaagaattc taccagtcta ggaataagag attgatatcg 126900 catagaaata caaaagttca taatctcatc atctaagagc attttgttac cattgtaata 126960 aatatccact ctgtcatatg tataaatgaa gtactgttca aacatgatga gatgtttata 127020 tgttggcata gtagtgagat ctacgtttgg taatggcaat gtattaagat taactccata 127080 atgtctagca gcatctgcga tgttataagc gttgtcaaag cggggtcgat cttgtgctgt 127140 tatatattgt ctaacaccta taagattatc aaaatcttgt ctgcttaata caccgttaac 127200 aatttttgcc ttgaattctt ttattggtgc attaataaca tccttataga ggatgttaaa 127260 caaataagtg ttatcaaagt taagatctgg atatttcttt tctgctagaa catccattga 127320 gtcggagcca tctggtttaa tataaccacc gataaatcta gctctgtatt ctgtatccgt 127380 caatctaata ttaagaaggt gttgagtgaa aggtggaaga tcgtaaaagc tgtgagtatt 127440 aatgatagga ttagtttccg aactaatgtt aattggggta ttaataatat ctatatttcc 127500 agcgttaagt gtaacattaa acagttttaa ttcacgtgac gtggtatcaa ttaaataatt 127560 aatgcccaat ttggatatag cagcctgaag ctcatcttgt ttagttacgg atcctaatga 127620 gttattaagc aatatatcga acggatgaac gaaggttgtt ttaagttggt cacatacttt 127680 gtaatctaga catagatgcg gaagaacggt agaaactata cgaaataaat attcagagtc 127740 ctctaattga tcaagagtaa ctattgactt aataggcatc atttatttag tattaaatga 127800 cgaccgtacc agtgacggat atacaaaacg atttaattac agagttttca gaagataatt 127860 atccatctaa caaaaattat gaaataactc ttcgtcaaat gtctattcta actcacgtta 127920 acaacgtggt agatagagaa cataatgccg ccgtagtgtc atctccagag gaaatatcct 127980 cacaacttaa tgaagatcta tttccagatg atgattctcc ggccactatt atcgaacgag 128040 tacaacctca tactactatt attgacgata ctccacctcc tacgtttcgt agagagttat 128100 tgatatcgga acaacgtcaa caacgagaaa aaagatttaa tattacagta tcgaaaaatg 128160 ctgaagcaat aatggaatct agatctatga tatcttctat gccaacacaa acaccatcct 128220 tgggagtagt ttatgataaa gataaaagaa ttcagatgtt ggaggatgaa gtggttaatc 128280 ttagaaatca acgatctaat acaaaatcat ctgataattt agataatttt accagaatac 128340 tatttggtaa gactccgtat aaatcaacag aagttaataa gcgtatagcc atcgttaatt 128400 atgcaaattt gaacgggtct cccttatcag tcgaggactt ggatgtttgt tcagaggatg 128460 aaatagatag aatctataaa acgattaaac aatatcacga aagtagaaaa cgaaaaatta 128520 tcgtcactaa cgtgattatt attgtcataa atattatcga gcaagcattg ctaaaactcg 128580 gatttgaaga aatcaaagga ctgagtaccg atatcacttc agaaattatc gatgtggaga 128640 tcggagatga ctgcgatgct gtagcatcaa aactaggaat cggtaacagt ccggttctta 128700 atattgtatt gtttatactc aagatattcg ttaaacgaat taaaattatt taatttaata 128760 cattcccata tccagacaac aatcgtctgg attaatctgt tcctgtcgtc tcataccgga 128820 cgacatatta atctttttat tagtaggcat ctttttagat ggtttctttt tcccagcatt 128880 aactgagtcg atacctagaa gatcgtgatt gatctctccg accattccac gaacttctaa 128940 ttggccgtct ctgacggtac cataaactat tttaccagca ttagtaacag cttggacaat 129000 ctgaccatcc atcgcattgt acgatgtagt agtaactgtt gttctacgtc taggagcacc 129060 agaagtattt ttggagccct tggatgttga tgtagaagaa gacgaggatt ttgattttgg 129120 tttacatgta atacattttg tatcacatgc gccggcagtc acatctgttt gagaattaag 129180 attattgttg cctcctttga cggctgcatc tccaccgatt tgcgctagta gatttttaag 129240 ctgtggtgta atcttattaa ctgtttcgat ataatcatcg taactgcttc taacggctaa 129300 atttttttta tccgccattt agaagctaaa aatattttta tttatgcaga agatttaact 129360 agattataca atgaactaat atgatccttt tccagattat ttacaaactt ggtatttttt 129420 ggttctggag gaggcgaatt taaattcgga cttggatttg gattttgtgg gttcttgatc 129480 ttattataca gcgcatatag gatggcgacg gtaactgcta cgcaaatacc gatcaacaaa 129540 agaataccaa tcatttatg acaataactt cactattgat caagtatgca atatatcatc 129600 ttttcactaa ataagtagta ataatgattc aacaatgtcg agatatatgg acgataataa 129660 tttagttcat ggaaatatcg ctatgattgg tatgaatgac tccgctaact ctgtggggcg 129720 cgcagtgctt tccccacata gaataaatta gcattccgac tgtgataata ataccaagta 129780 taaacgccat aatactcaat actttccatg tacgagtggg actggtagac ttactaaagt 129840 caataaaggc gaagatacac gaaagaatca aaagaatgat tccagcgatt agcacgccgg 129900 aaaaataatt tccaatcata agcatcatat ccatttaact aataaaaatt ttaaatcgcc 129960 gaatgaacaa agtggaatat aaaccatata aaaacaatag tttgtactgc aaaaataata 130020 tctatttttg ttttcgaaga tatggtaaaa ttaaatagta gtacacagca tgttataact 130080 aacagcagca acggctcgta attacttatc attactaga cgaaaaggtg gtgggatatt 130140 ttcttgctca aataatacga atatatcacc catccatttt atgcgatgtt tatatactct 130200 aatctttaat agatctatag acgacgggtt taccaacaat atagatttta tcgattcatc 130260 taatttaaac ccttccttaa acgtgaatga tctattatct ggcataacga tgactctacc 130320 cgatgaatcg gacaatgtac tgggccatgt agaataaatt atcaacgaat tatcgtctac 130380 gaacatttat atcatttgtt ttaattttag tacgcgaata aatagatata aaatagaaaa 130440 taacagatat tacaaccaat gttatggccg cgcccaacca ggtaggcagt tttatttat 130500 cttttactac aggttctcct ggatgtacgt caccaacggc ggacgtagtt ctagtacaat 130560 tagacgtaag ttccgcttgg gaatttttta acgctaaaga gttaacgtta atcgtgcacc 130620 caacgtattt acatctagtt ctttgaacat cttgattata atataaccat tttctatctc 130680 tagattcgtc ggtgcactca tgtaaccaac ataccctagg tcctaaatat ttatctccgg 130740 aattagattt tggataattc gcgcaccaac aatttctatt tcctttatga tcgttacaaa 130800 agacgtataa tgccgtatcc ccaaaagtaa aataatcagg acgaataatt ctaataaact 130860 cagaacaata tctcgcatcc atatgtttgg agcaaatatc ggaataagta gacatagccg 130920 gtttccgttt tgcacgtaac cattctaaac aattggggtt tccaggatcg tttctacaaa 130980 atccagtcat gaaatcatca caatgttctg tcttgtaatt attattaaat atttttggac 131040 agtgtttggt atttgtctta gaacaacatt ttgccacgct atcactatcg cccaggagat 131100 aatccttttt tataaaatga catcgttgcc cggatgctat ataatcagtg gcgtgtttta 131160 aatccttaat atattcagga gttacctcgt tctgataata gattaatgat ccaggacgaa 131220 atttgaaaga actacatggt tctccatgaa ttaatacata ttgtttagca aattcaggaa 131280 ctataaaact actacaatga tctatcgaca taccatctat caaacaaaac ttgggtttaa 131340 tttctcccgg agatgtttca taatagtacg tataactttc ttctgcaaac ttaacagctc 131400 tattatattc aggataatta aaacctaatt ccatatattt gtctcgtata tctgctattc 131460 ctggtgctat tttaattcta ttaagagtaa cggctgcccc cattcttaat aatcgtcagt 131520 atttaaactg ttaaatgttg gtatatcaac atctacctta tttcccgcag tataaggttt 131580 gttgcaggta tactgttcag gaatggttac atttatactt cttctatagt cctgtctttc 131640 gatgttcatc acatatgcaa agaacagaat aaacaaaata atgtaagaaa taatattaaa 131700 tatctgtgaa ttcgtaaata cattgattgc cataataatt acagcagcta caatacatac 131760 aatagacatt cccacagtgt tgccattacc tccacgatac atttgagtta ctaagcaata 131820 ggtaataact aagctagtaa gaggcaatag aaaagatgag ataaatatca tcaatataga 131880 gattagagga gggctatata gagccaagac gaacaaaatc aaaccgagta acgttctaac 131940 atcattattt ttgaagattc ccaaataatc attcattcct ccataatcgt tttgcattat 132000 acctccatct ttaggcataa acgattgctg ctgttcctct gtaaataaat ctttatcaag 132060 cactccagca cccgcagaga agtcgtcaag catattgtaa tatcttaaat aactcattta 132120 tatattaaaa aatgtcacta ttaaagatgg agtataatct ttatgccgaa ctaaaaaaaa 132180 tgacttgtgg tcaaccccta agtcttttta acgaagacgg ggatttcgta gaagttgaac 132240 cgggatcatc ctttaagttt ctgataccta agggatttta cgcctctcct tccgtaaaga 132300 cgagtctagt attcgagaca ttaacaacga ccgataataa aatcactagt atcaatccaa 132360 caaatgcgcc aaagttatat cctcttcaac gcaaagtcgt atctgaagta gtttctaata 132420 tgaggaaaat gatcgaatca aaacgtcctc tatacattac tcttcacttg gcgtgtggat 132480 ttggtaagac tattaccacg tgttatctta tggctacaca cggtagaaaa accgtcattt 132540 gcgtacccaa taaaatgtta atacatcaat ggaagacaca ggtagaggca gtcggattgg 132600 aacataagat atctatagat ggagtaagta gtctattaaa ggaactaaag actcaaagtc 132660 cggatgtatt aatagtagtc agtagacatc tgacaaacga tgccttttgt aaatatatca 132720 ataagcatta tgatttgttc atcttggatg aatcacatac gtataatctg atgaacaata 132780 cagcagttac aagattttta gcgtattatc ctccgatgat gtgttatttt ttaactgcta 132840 cacctagacc agctaaccga atttattgta acagtattat taatattgcc aagttatccg 132900 atctaaaaaa aactatctat gcggtagata gtttttttga gccatattcc acagacaata 132960 ttagacatat ggtaaaacga ctagatggac catctaataa atatcatata tatactgaga 133020 agttattatc tgtagacgag cctagaaatc aacttattct tgataccctg gtagaagaat 133080 tcaagtcagg aactattaat cgaattttag ttattactaa actacgtgaa catatggtat 133140 tcttctacaa acgattatta gattttttcg gatcagaggt tgtatttata ggagacgccc 133200 aaaatagacg tactccagat atggtcaaat caatcaagga actaaataga tttatattcg 133260 tatccacctt atttattcc ggtactggtt tagatattcc tagtttggat tcgttgttca 133320 tttgctcggc agtaatcaac aatatgcaaa tagagcaatt actagggagg gtatgtcgag 133380 aaacagaact attagatagg acggtatatg tatttcctaa cacatccatc aaagaaataa 133440 agtacatgat aggaaatttc atgcaacgaa ttattagtct gtctgtagat aaactaggat 133500 ttaaacaaaa aagttatcgg aaacatcaag aatccgatcc cacttctgta tgtacaacat 133560 cctccagaga agaacgtgta ttaaatagaa tatttaactc gcaaaatcgt taagaagttt 133620 aagcgacgat ccgcatgctg cgcaggccag tgtattaccc ctcatagtat taatataatc 133680 caatgatact tttgtgatgt cggaaatctt aaccaattta gactgacagg cagaacacgt 133740 catgcaatca tcatcgtcat cgataactgt agtcttgggc ttctttttgc ggctcttcat 133800 tccggaacgc acattggtgc tatccattta ggtagtaaaa aataagtcag aatatgccct 133860 atagcacgat cgtgcaaaac ctggtatatc gtctctatct ttatcacaat atagtgtatc 133920 gacattttta ttatattga cctcgtttat cttggaacat ggaatgggaa catttttgtt 133980 atcaacggcc atctttgcct taattccaga tgttgtaaaa ttataactaa acagtctatc 134040 atcgacacaa atgaaattct tgtttagacg tttgtagttt acgtatgcgg ctcgttcgcg 134100 tctcattttt tcagatattg caggtactat aatattaaaa ataagaatga aataacatag 134160 gattaaaaat aaagttatca tgacttctag cgctgattta actaacttaa aagaattact 134220 tagtctgtac aaaagtttga aattttcaga ttctgcggct atagaaaagt ataattcttt 134280 ggtagaatgg ggaacatcta cttactggaa aataggcgtg caaaaggtag ctaatgtcga 134340 gacgtcaata tctgattatt atgatgaggt aaaaaataaa ccgtttaata ttgatccggg 134400 atattacatt ttcttaccgg tatattttgg aagcgtcttt atttatcga agggtaaaaa 134460 tatggtagaa cttggatctg gaaactcttt tcaaatacca gatgatatgc gaagtgcgtg 134520 taacaaagta ttagacagcg ataacggaat agactttctg agatttgttt tgttaaacaa 134580 tagatggata atggaagatg ctatatcaaa atatcagtct ccagttaata tatttaaact 134640 agctagtgag tacggattaa acatacccaa atatttagaa attgaaatag aggaagacac 134700 attatttgac gacgagttat actctattat agaacgctct ttcgatgata aatttccaaa 134760 aatatccata tcgtatatta agttgggaga acttagacgg caagttgtag actttttcaa 134820 attctcgttc atgtatattg agtccatcaa ggtagatcgt ataggagata atatttttat 134880 tcctagcgtt ataacaaaat caggaaaaaa gatattagta aaagatgtag accatttaat 134940 acgatccaag gttagagaac atacatttgt aaaagtaaaa aagaaaaaca cattttccat 135000 tttatacgac tatgatgggaa acggaacaga aactagagga gaagtaataa aacgaattat 135060 agacactata ggacgagact attatgttaa cggaaagtat ttctctaagg ttggtagtgc 135120 aggcttaaag caattgacta ataaattaga tattaatgag tgcgcaactg tcgatgagtt 135180 agttgatgag attaataaat ccggaactgt aaaacgaaaa ataaaaaacc aatcagcatt 135240 tgatttaagc agagaatgtt tgggatatcc agaagcggat tttataacgt tagttaataa 135300 catgcggttc aaaatagaaa attgtaaggt tgtaaatttc aatattgaaa atactaattg 135360 tttaaataac ccgagtattg aaactatata tggaaacttt aaccagttcg tctcaatctt 135420 taatatcgtc accgatgtca aaaaaagatt attcgagtga aataatatgc gcctttgata 135480 taggtgcaaa aaatcctgcc agaactgttt tagaagtcaa ggataactcc gttaggggtat 135540 tggatatatc aaaattagac tggagttctg attgggaaag gcgcatagct aaagatttgt 135600 cacaatatga atacactaca gttcttctag aacgtcagcc tagaaggtcg ccgtacgtca 135660 aatttatcta ttttattaaa ggctttttat atcatacatc ggctgccaaa gttatttgcg 135720 tctcgcctgt catgtctggt aattcatata gagatcgaaa aaagagatcg gtcgaagcat 135780 ttcttgattg gatggacaca ttcggattgc gagactccgt tccggataga cgcaaattag 135840 acgatgtagc ggatagtttc aatttggcta tgagatacgt attagataaa tggaatacta 135900 attatacacc ttataatagg tgtaaatcta gaaattacat aaaaaaaatg taataacgtt 135960 agtaacgcca ttatggataa tctatttacc tttctacatg aaatagaaga tagatatgcc 136020 agaactattt ttaactttca tctaataagt tgcgatgaaa taggagatat atatggtctt 136080 atgaaagaac gcatttcctc agaggatatg tttgataata tagtgtataa taaagatata 136140 catcatgcca ttaagaaact agtgtattgc gacatccaac ttactaaaca cattattaat 136200 cagaatacgt atccggtatt taacgattct tcacaagtga aatgttgtca ttatttcgac 136260 ataaactcag ataatagcaa tattagctct cgtacagtag agatatttga gagggaaaag 136320 tcatctcttg tatcatatat taaaactacc aataagaaga gaaaggtcaa ttacggcgaa 136380 ataaagaaaa ctgttcatgg aggcactaat gcaaattact tttccggtaa aaagtctgac 136440 gagtatctga gtactacagt tagatccaac attaatcaac cttggatcaa aaccatctct 136500 aagaggatga gagttgatat cattaatcac tctatagtaa cgcgtggaaa aagctctata 136560 ttacaaacta tagaaattat ttttactaat agaacatgtg tgaaaatatt caaggattct 136620 actatgcaca ttattctatc caaggacaag gatgaaaagg ggtgtataca catgattgac 136680 aaattattct atgtctatta taatttattt ctgttgttcg aggatatcat ccaaaacgag 136740 tactttaaag aagtagctaa tgttgtaaac cacgtactta cggctacggc attagatgag 136800 aaattattcc taattaagaa aatggctgaa cacgatgttt atggagttag caatttcaaa 136860 atagggatgt ttaacctgac atttattaag tcgttggatc ataccgtttt cccctctctg 136920 ttagatgagg atagcaaaat aaagtttttt aaggggaaaa agctcaatat tgtagcatta 136980 cgatctctgg aggattgtat aaattacgtg actaaatccg agaatatgat agaaatgatg 137040 aaggaaagat cgactatttt aaatagcata gatatagaaa cggaatcggt agatcgtcta 137100 aaagaattgc ttctaaaatg aaaaaaaaca ctgattcaga aatggatcaa cgactcggat 137160 ataagttttt ggtgcctgat cctaaagccg gagtttttta tagaccgtta catttccaat 137220 atgtatcgta ttctaatttt atattgcatc gattgcatga aatcttgacc gtcaagcggc 137280 cactcttatc gtttaagaat aatacagaac gaattatgat agaaattagc aatgttaaag 137340 tgactcctcc agattactca cctataatcg cgagtattaa aggtaagagt tatgacgcat 137400 tagccacgtt cactgtaaat atctttaaag aggtaatgac caaagagggt atatccatca 137460 ctaaaataag tagttatgag ggaaaagatt ctcatttgat aaaaattccg ctactaatag 137520 gatacgggaa taaaaatcca cttgatacag ccaagtatct tgttcctaat gtcataggtg 137580 gagtctttat caataaacaa tctgtcgaaa aagtaggaat taatctagta gaaaagatta 137640 caacatggcc aaaatttagg gttgttaagc caaactcatt cactttctcg ttttcctccg 137700 tatcccctcc taatgtatta ccgacaagat atcgccatta caagatatct ctggatatat 137760 cacaattgga agcgtcgaat atatcatcga caaagacatt tataacggtc aatattgttt 137820 tgctgtctca atatttatct agagtgagtc tagaattcat tagacgtagc ttatcatacg 137880 atatgcctcc agaagttgtc tatctagtaa acgcgataat agatagtgct aaacgaatta 137940 ctgaatctat tactgacttt aatattgata catacattaa tgacctggtg gaagctgaac 138000 acattaaaca aaaatctcag ttaacgatca acgagttcaa atatgaaatg ctgcataact 138060 ttttacctca tatgaactat acacccgatc aactaaaggg attttatatg atatctttac 138120 taagaaagtt tctctactgt atctaccaca cttctagata tccagataga gattcgatgg 138180 tttgtcatcg tatactaaca tacggcaaat attttgagac gttggcacat gatgaattag 138240 agaattacat aggcaacatc cgaaacgata tcatgaacaa tcacaagaac agaggcactt 138300 acgcggtaaa cattcatgta ctaacaactc ctggacttaa tcatgcattt tctagtctat 138360 tgagtggaaa gttcaaaaag tcagacggta gttatcgaac acatcctcac tattcatgga 138420 tgcagaatat ttctattcct aggagtgttg gattttatcc ggatcaagta aagatttcaa 138480 agatgttttc tgtcagaaaa taccatccaa gtcaatatct ttacttttgt tcatcggacg 138540 ttccggaaag aggtcctcag gtaggtttag tatctcaatt gtctgtcttg agttccatta 138600 caaatatact aacgtctgag tatttggatt tggaaaagaa aatttgtgag tatatcagat 138660 catattataa agatgatata agttactttg aaacaggatt tccaatcact atagaaaatg 138720 ctctagtcgc atctcttaat ccaaatatga tatgtgattt tgtaactgac tttagacgta 138780 gaaaacggat gggattcttc ggtaacttgg aggtaggtat tactttagtt agggatcaca 138840 tgaatgaaat tcgcattaat attggagcgg gaagattagt cagaccattc ttggttgtgg 138900 ataacggaga gctcatgatg gatgtgtgtc cggagttaga aagcagatta gacgacatga 138960 cattctctga cattcagaaa gagtttccgc atgtcatcga aatggtagat atagaacaat 139020 ttacttttag taacgtatgt gaatcggttc aaaaatttag aatgatgtca aaggatgaaa 139080 gaaagcaata cgatttatgt gactttcctg ccgaatttag agatggatat gtagcatctt 139140 cactagtggg aatcaatcac aattctggac ccagagctat tcttggatgt gctcaagcta 139200 aacaagctat ctcttgtctg agctcggata tacgaaataa aatagacaat ggaattcatt 139260 tgatgtatcc agagaggcca atcgtgatta gtaaggcttt agaaacttca aagatgcgg 139320 ctaattgctt cggccaacat gttactatag cattaatgtc gtacaaaggt atcaatcaag 139380 aggatggaat tatcatcaaa aaacaattta ttcagagagg cggtctcgat attgttacag 139440 ccaagaaaca tcaagtagaa attccgttgg aaaactttaa taacaaagaa agagataggt 139500 ctaacgccta ttcaaaatta gaaagtaatg gattagttag actgaatgct ttcttggaat 139560 ccggagacgc tatagcacga aatatctcat caagaactct tgaagatgat tttgctagag 139620 ataatcagat tagctttgat gtttccgaaa aatataccga tatgtacaaa tctcgcgttg 139680 aacgagtaca agtagaactt actgacaaag ttaaggtacg agtattaacc atgaaagaaa 139740 gaagacccat tctaggagac aaatttacca ctagaacgag tcaaaaggga acagtcgcgt 139800 atatcgcgga tgaaacggaa cttccatacg atgaaaatgg tatcacacca gatgtcatta 139860 ttaattctac atccatcttc tctagaaaaa ctatatctat gttgatagag gttattttaa 139920 cagccgcata ttctgctaag ccgtacaaca ataagggaga aaaccgacct gtctgttttc 139980 ctagtagtaa cgaaacatcc atcgatacat atatgcaatt cgctaaacaa tgttatgagc 140040 attcaaatcc gaaattgtct gatgaagaat tatcggataa aatcttttgt gaaaagattc 140100 tctatgatcc tgaaacggat aagccttatg catccaaagt attttttgga ccaatttatt 140160 acttgcgtct gaggcattta actcaggaca aggcaaccgt tagatgtaga ggtaaaaaga 140220 cgaagctcat tagacaggcg aatgagggac gaaaacgtgg aggaggtatc aagttcggag 140280 aaatggagag agactgttta atagcgcatg gtgcagccaa tactattaca gaagttttga 140340 aagattcgga agaagattat caagatgtgt atgtttgtga aaattgtgga gacatagcag 140400 cacaaatcaa gggtattaat acatgtctta gatgttcaaa acttaatctc tctcctctct 140460 taacaaaaat tgataccacg cacgtatcta aagtatttct tactcaaatg aacgccagag 140520 gcgtaaaagt taaattagat ttcgaacgaa ggcctccttc gttttataaa ccattagata 140580 aagttgatct caaaccgtct tttctggtgt aatattctag tttggtagta gatacatatc 140640 aatatcatca aattcgagat ccgaattata aaatgggcgt ggattgttaa ctatagaatc 140700 ggacgtctga tattcgaaaa tctgtggagt tttaggtttt ggtggaggtg taactgctac 140760 ttgggatact gaagtctgat attcagaaag ctgggggatg ttctggttcg acatccaccg 140820 atggtgtcac atcactaatc ggttcggtaa cgtctgtgga cgatggaggc accacttcta 140880 caggttctgg ttctttatcc tcagtcatca acggagctac ttcaatgcga ggaaatgtat 140940 aatttggtaa tggtttctca tgtggatctg aagaagaggt aagatatcta ctagaaagat 141000 accgatcacg ttctagttct ctttgtaga acttaacttt ttctttctcc gcatctagtt 141060 gatattccaa cctcttcacg ttactacgtt cagattccaa ttcacgttcg catgggttac 141120 ctccgcagtt tttacgagcg atttcacgtt cagccttcat gcgtcttata gcatgaattc 141180 gcttatcgtt atcgggttta gcttctgtca ccttagcaat tcctttttta ttaaactcta 141240 cataatcata tccatttcta ttgtttgttc taatataaac gagtatagca tcattgctaa 141300 atttttcaat agtatcgaaa acagaatatc ctaaaccata taatatatat tcaggaacac 141360 tcaaactaaa tgtccaggat tctcctaaat acgtaaactt taatagtgcg aaatcattca 141420 aaaatctacc acttatagat agatagatag tacataaatg cgtatagtag tctacctatc 141480 tctttattat gaaaaccggc attacgatca tatatgtcgt gatatacctg tgatccgttt 141540 acgttaaacc ataaatacat gggtgatcct ataaacatga atttattct aattctcaga 141600 gctatagtta attgaccgtg taatatttgc ttacatgcat acttgatacg atcattaata 141660 agatttttat cattgctcgt tatttcagaa tcgtatatat aaggagtacc atcgtgattc 141720 ttaccagata ttatacaaaa tactatatat aaaatatatt gacccacgtt agtaatcatg 141780 taaatgttta acgttttaaa ttttgtattc aatgatccat tatcatacgc tagcatggtc 141840 ttatgatatt cattctttaa aatataatat tgtgttagcc attgcattgg ggctcctaat 141900 ggagattttt tattctcatc cattttagga taggctttca taaagtccct aataacttcg 141960 tgaataatgt ttctatgttt tctactgatg catgtatttg cttcgatttt tttatcccat 142020 gtttcatcta tcatagattt aaacgcagta atgctcgcaa cattaacatc ttgaaccgtt 142080 ggtacaattc cgttccataa atttataatg ttcgccattt atataactca ttttttgaat 142140 atacttttaa ttaacaaaag agttaagtta ctcatatgga cgccgtccag tctgaacatc 142200 aatcttttta gccagagata tcatagccgc tcttagagtt tcagcgtgat tttccaacct 142260 aaatagaact tcatcgttgc gtttacaaca cttttctatt tgttcaaact ttgttgttac 142320 attagtaatc tttttttcca aattagttag ccgttgtttg agagtttcct cattgtcgtc 142380 ttcatcggct ttaacaattg cttcgcgttt agcctctggc tttttagcag ccgttgtaga 142440 aaaaaattca gttgctggaa ttgcaagatc gtcatctccg gggaaaagag ttccgtccat 142500 ttaaagtaca gattttagaa actgacactc tgcgttattt atatttggta caacacatgg 142560 attataaata ttgatgttaa taacatcaga aaatgtaaag tctatacatt gttgcatcgt 142620 gttaaatttt ctaatggatc tagtattatt gggtccaact tctgcctgaa atccaaatat 142680 ggaagcggat acaaaaccgt ttcctggata aaccacacat ctccactttt gctttacatc 142740 agaaattgtg tcgttgacat cttgaactct cctactaat gccggtgttc cacctataga 142800 ttttgaatat tcgaatgctg catgagtagc attaaattcc ttaatattgc cataattttc 142860 atatattgag taaccctgga taaaaagtaa acacaccgca gccgtagcta ccacaataaa 142920 aaaaattgat agagagttca tttataatct attagaagct gacaaaattt ttttacacgc 142980 atcagacaat gctttaataa atagttcaac atctactttt gtcatatcga accgatggta 143040 tgattctaac ctagaattac atccgaaaaa gttgactatg ttcatagtca ttaagtcatt 143100 aacaaacaac attccagact ctggattata agacgatact gtttcgtcac aattacctac 143160 cttaatcatg tgattatgaa tattggctat tagagcacct tctaagaaat ctataatatc 143220 tttgaaacac gatttaaaat caaaccacga atatacttct acgaagaaag ttagtttacc 143280 cataggagaa ataactataa atggagatct aaatacaaaa tccggatcta tgatagtttt 143340 aacattatta tattctctat taaatacctc cacatctaaa aatgttaatt ttgaaactat 143400 gtcttcgttt attaccgtac ctgaactaaa cgctataagc tctattgttt gagaactctt 143460 taaacgatat tcttgaaata catgtaacaa agtttccttt aactcggtcg gtttatctac 143520 catagttaca gaatttgtat ccttatctat aatataataa tcaaaatcgt ataaagttat 143580 ataattatcg cgttcagatt gggatctttt caaatagact aaaaacccca tttctctagt 143640 aagtatctta tgtatatgtt tgtaaaatat cttcatggtg ggaatatgct ctaccgcagt 143700 tagccattcc tcattgacag cggtagatgt attagacaaa actattccaa tgtttaacaa 143760 gggccatttt acgagattat taaatccttg tttgataaat gtagccaatg agggttcgag 143820 ttcaacgacg attgaattct cttcccgcgg atgctgcatg atgaacgacg ggatgttgtt 143880 cgattgattt ggaattcttt ttcgactttt tgtttatatt aaatatttta aaatttatag 143940 cggatagcaa ttcatgtacc acggataatg tagacgcgta ttgcgcatcg atatctttat 144000 tattagataa atttatcaat aaatgtgaga agtttgcctc gttaaggtct tccatttaaa 144060 tattatataa acatttgtgt ttgtatctta ttcgtctttt atggaatagt ttttactag 144120 taaagctgca attacacact ttgtccgtaa aacataaata taaacaccag cttttatcaa 144180 tcgttccaaa aagtcgacgg cggacatttt taacatggca tctattttaa atacacttag 144240 gtttttggaa aaaacatcat tttataattg taacgattca ataactaaag aaaagattaa 144300 gattaaacat aagggaatgt catttgtatt ttataagcca aagcattcta ccgttgttaa 144360 atacttgtct ggaggaggta tatatcatga tgatttggtt gtattgggga aggtaacaat 144420 taataatcta aagatgatgc tattttacat ggatttatca tatcatggag tgacaagtag 144480 tggagcaatt tacaaattgg gatcgtctat cgatagactt tctctaaata ggactattgt 144540 tacaaaagtt aataattatg atgatacatt ttttgacgac gatgattgat cgctattgca 144600 caattttgtt tttttacttt ctaatatagc gtttagattc tttttcatgt gcgaatattg 144660 atttactaaa atatcgatgt ttaacttttg ttctatgacg tccttatcag cggtatcggt 144720 acatatacgt aattcacctt cacaaaatac ggagtcttcg ataataatag ccaatcgatt 144780 attggatcta gctgtctgta tcatattcaa catgtttaat atatcctttc gtttcccctt 144840 tacaggcatc gatcgtagca tattttccgc gtctgagatg gaaatgttaa aactacaaaa 144900 atgcgtaatg ttagcccgtc ctaatattgg tacgtgtcta taagtttggc atagtagaat 144960 aatagacgtg tttaaatgcc ttccaaagtt taagaattct attagagtat tgcattttga 145020 tagtttatca cctacatcat caaaaataag taaaaagtgt gctgattttt tatgattttg 145080 tgcgacagca atacattttt ctatgttact tttagttcgt atcagattat attctagaga 145140 ttcctgacta ctaacgaaat taatatgatt tggccaaatg tatccatcat aatctgggtt 145200 ataaacgggt gtaaacaaga atatatgttt atatttttta actagtgtag aaaacagaga 145260 tagtaaatag atagtttttc cagatccaga tcctcccgtt aaaaccattc taaacggcat 145320 ttttaataaa ttttctcttg aaaattgttt ttcttggaaa caattcataa ttatatttac 145380 agttactaaa ttaatttgat aataaatcaa aatatggaaa actaaggtcg ttagtaggga 145440 ggagaacaaa gaaggcacat cgtgacataa ataacattta ttatcatgat gacaccagaa 145500 aacgacgaag agcagacatc tgtgttctcc gctactgttt acggagacaa aattcaagga 145560 aagaataaac gcaaacgcgt gattggtcta tgtattagaa tatctatggt tatttcacta 145620 ctatctatga ttaccatgtc cgcgtttctc atagtgcgcc taaatcaatg catgtctgct 145680 aacgaggctg ctattactga cgccgctgtt gccgttgctg ctgcatcatc tactcataga 145740 aaggttgcgt ctagcactac acaatatgat cacaaagaaa gctgtaatgg tttatattac 145800 cagggttctt gttatatatt acattcagac taccagttat tctcggatgc taaagcaaat 145860 tgcactgcgg aatcatcaac actacccaat aaatccgatg tcttgattac ctggctcatt 145920 gattatgttg aggatacatg gggatctgat ggtaatccaa ttacaaaaac tacatccgat 145980 tatcaagatt ctgatgtatc acaagaagtt agaaagtatt tttgtgttaa aacaatgaac 146040 taatatttat ttttgtacat taataaatga aatcgcttaa tagacaaact gtaagtaggt 146100 ttaagaagtt gtcggtgccg gccgctataa tgatgatact ctcaaccatt attagtggca 146160 taggaacatt tctgcattac aaagaagaac tgatgcctag tgcttgcgcc aatggatgga 146220 tacaatacga taaacattgt tatttagata ctaacattaa aatgtctaca gataatgcgg 146280 tttatcagtg tcgtaaatta cgagccagat tgcctagacc ggatactaga catctgagag 146340 tattgtttag tattttttat aaagattatt gggtaagttt aaaaaagacc aatgataaat 146400 ggttagatat taataatgat aaagatatag atattagtaa attaacaaat tttaaacaac 146460 taaacagtac gacggatgct gaagcgtgtt atatatacaa gtctggaaaa ctggttaaaa 146520 cagtatgtaa aagtactcaa tctgtactat gtgttaaaaa attctacaag tgacaacaaa 146580 aaatgaatta ataataagtc gttaacgtac gccgccatgg acgccgcgtt tgttattact 146640 ccaatgggtg tgttgactat aacagataca ttgtatgatg atctcgatat ctcaatcatg 146700 gactttatag gaccatacat tataggtaac ataaaaactg tccaaataga tgtacgggat 146760 ataaaatatt ccgacatgca aaaatgctac tttagctata agggtaaaat agttcctcag 146820 gattctaatg atttggctag attcaacatt tatagcattt gtgccgcata cagatcaaaa 146880 aataccatca tcatagcatg cgactatgat atcatgttag atatagaaga taaacatcag 146940 ccattttatc tattcccatc tattgatgtt tttaacgcta caatcataga agcgtataac 147000 ctgtatacag ctggagatta tcatctaatc atcaatcctt cagataatct gaaaatgaaa 147060 ttgttgttta attcttcatt ctgcatatca gacggcaatg gatggatcat aattgatggg 147120 aaatgcaata gtaatttttt atcataaaag ttgtaaagta aataataaaa caataaatat 147180 tgaactagta gtacgtatat tgagcaatca gaaatgatgc tggtacctct tatcacggtg 147240 accgtagttg cgggaacaat attagtatgt tatatattat atatttgtag gaaaaagata 147300 cgtactgtct ataatgacaa taaaattatc atgacaaaat taaaaaagat aaagagttct 147360 aattccagca aatctagtaa atcaactgat agcgaatcag actgggagga tcactgtagt 147420 gctatggaac aaaacaatga cgtagataat atttctagga atgagatatt ggacgatgat 147480 agcttcgctg gtagtttaat atgggataac gaatccaatg tcatggcgcc tagcacagaa 147540 cacatttacg atagtgttgc tggaagcacg ctgctaataa ataatgatcg taatgaacag 147600 actatttatc agaacactac agtagtaatt aatgagacgg agactgttga agtacttaat 147660 gaagatacca aacagaatcc taactattca tccaatcctt tcgtaaatta taataaaacc 147720 agtatttgta gcaagtcaaa tccgttcatt acagaactca acaataaatt tagtgagaat 147780 aatccgttta gacgagcaca tagcgatgat tatcttaata agcaagaaca agatcatgaa 147840 cacgatgata tagaatcatc ggtcgtatca ttggtgtgat tagtttcctt tttataaaat 147900 tgaagtaata tttagtatta ttgctgccgt cacgttgtac aaatggagat attccctgta 147960 ttcggcattt ctaaaattag caattttatt gctaataatg actgtagata ttatatagat 148020 acagaacatc aaaaaattat atctgatgag atcaatagac agatggatga aacggtactt 148080 cttaccaaca tcttaagcgt agaagttgta aatgacaatg agatgtacca tcttattccc 148140 catagactat cgactattat actctgtatt agttctgtcg gaggatgtgt tatctctata 148200 gataatgaca tcaatgacaa aaatattcta acatttccca ttgatcatgc tgtaatcata 148260 tccccactga gtaaatgtgt cgtagttagc aagggtccta caaccatatt ggttgttaaa 148320 gcggatatac ccagcaaacg attggtaaca tcgtttacaa acgacatact gtatgtaaac 148380 aatctgtcac tgattaatta tttgccgttg tctgtattca ttattagacg agtcaccgac 148440 tatttggata gacacatatg cgatcagata tttgcgaata ataagtggta ttccattata 148500 accatcgacg ataagcaata tcctattcca tcaaactgta taggtatgtc ctctgccaag 148560 tacataaatt ctagcatcga gcaagatact ttaatacatg tttgtaacct cgagcatcca 148620 ttcgacttag tatacaaaaa aatgcagtcg tacaattctg tacctatcaa ggaacaaata 148680 ttgtacggta gaattgataa tataaatatg agcattagta tttctgtgga ttaatagatt 148740 tctagtatgg ggatcattaa tcatctctaa tctctaaata cctcataaaa cgaaaaaaaa 148800 gctattatca aatactgtac ggaatggatt cattctcttc tctttttatg aaactctgtt 148860 gtatatctac tgataaaact ggaagcaaaa aatctgataa aaagaataag aataagatca 148920 aggattatat ggaacacgat tattataaaa taacaatagt tcctggttcc tcttccacgt 148980 ctactagctc gtggtattat acacatgcct agtaatagtc tctttgcgtt gacggaaagc 149040 agactagaaa taacaggcta aaatgttcag acaccataat agttcccaac ccagataata 149100 acagagtacc atcaacacat tcctttaaac tcaatcccaa acccaaaacc gttaaaatgt 149160 atccggccaa ttgatagtag ataatgaggt gtacagcgca tgataattta cacagtaacc 149220 aaaatgaaaa tactttagta attataagaa atatagatgg taacgtcatc atcaacaatc 149280 caataatatg ccggagagta aacattgacg gataaaacaa aaatgctccg cataactcta 149340 tcatggcaat aacacaacca aatacttgta agattcctaa attagtagaa aatacaacgg 149400 atatcgatgt ataagtgatc tcgagaaata ataagaataa agtaatgccc gtaaagataa 149460 acatcaacat tgtttggtaa tcattaaacc aattagtatg aagttgaact aatttcacag 149520 tagattttat tccagtatta tccccgcatg tatacgtacc tggtaagata tctttatatt 149580 ccataatcaa tgagacatca ctatctgata acgaatgaag tctagcacta gtatgccatt 149640 tacttaatat ggtcgtcttg gaagttttat tataagttaa aatatcatgg ttatccaatt 149700 tccatctaat atactttgtc ggattatcta tagtacacgg aataatgatg gtatcattac 149760 atgctgtata ctctatggtc tttgtagttg ttataacaac caacgtatag aggtatatca 149820 acgatattct aactcttgac attttttatt tatttaaaat gatacctttg ttatttattt 149880 tattctattt tgctaacggt attgaatggc ataagtttga aacgagtgaa gaaataattt 149940 ctacttactt attagacgac gtattataca cgggtgttaa tggggcggta tacacatttt 150000 caaataataa actaaacaaa actggtttaa ctaataataa ttatatcaca acatctataa 150060 aagtagagga tgcggataag gatacattag tatgcggaac caataacgga aatcccaaat 150120 gttggaaaat agacggttca gacgacccaa aacatagagg tagaggatac gctccttatc 150180 aaaatagcaa agtaacgata atcagtcaca acggatgtgt actatctgac ataaacatat 150240 caaaagaagg aattaaacga tggagaagat ttgacggacc atgtggttat gatttataca 150300 cggcggataa cgtaattcca aaagatggtt tacgaggagc attcgtcgat aaagacggta 150360 ctttgacaa agtttacatt cttttcactg atactatcgg ctcaaagaga attgtcaaaa 150420 ttccgtatat agcacaaatg tgcctaaacg acgaaggtgg tccatcatca ttgtctagtc 150480 atagatggtc gacgtttctc aaagtcgaat tagaatgtga tatcgacgga agaagttata 150540 gacaaattat tcattctaga actataaaaa cagataatga tacgatacta tatgtattct 150600 tcgatagtcc ttattccaag tccgcattat gtacctattc tatgaatacc attaaacaat 150660 ctttttctac gtcaaaattg gaaggatata caaagcaatt gccgtctcca gctcctggta 150720 tatgtttacc agctggaaaa gttgttccac ataccacgtt tgaagtcata gaaaaatata 150780 atgtactaga tgatattata aagcctttat ctaaccaacc tatcttcgaa ggaccgtctg 150840 gtgttaaatg gttcgatata aaggagaagg aaaatgaaca tcgggaatat agaatatact 150900 tcataaaaga aaattctata tattcgttcg atacaaaatc taaacaaact cgtagctcgc 150960 aagtcgatgc gcgactattt tcagtaatgg taacttcgaa accgttattt atagcagata 151020 tagggatagg agtaggaatg ccacaaatga aaaaaatact taaaatgtaa tcttaatcga 151080 gtacaccaca cgacaatgaa caaacataag acagattatg ctggttatgc ttgctgcgta 151140 atatgcggtc taattgttgg aattattttt acagcgacac tattaaaagt tgtagaacgt 151200 aaattagttc atacaccatc aatagataaa acgataaaag atgcatatat tagagaagat 151260 tgtcctactg actggataag ctataataat aaatgtatcc atttatctac tgatcgaaaa 151320 acctgggagg aaggacgtaa tgcatgcaaa gctctaaatc caaattcgga tctaattaag 151380 atagagactc caaacgagtt aagtttttta agaagcatta gacgcggata ttgggtagga 151440 gaatccgaaa tattaaacca gacaacccca tataatttta tagctaagaa tgccacgaag 151500 aatggaacta aaaaacggaa atatatttgt agcacaacga atactcccaa actgcattcg 151560 tgttacacta tataacaatt acactacatt tttatcatac cactacttcg gttagatgtt 151620 ttagaaaaaa ataaatatcg ccgtaccgtt cttgttttta taaaaataac aattaacaat 151680 tatcaaattt tttctttaat attttacgtg gttgaccatt cttggtggta aaataatctc 151740 ttagtgttgg aatggaatgc tgtttaatgt ttccacactc atcgtatatt ttgacgtatg 151800 tagtcacatc gtttacgcaa tagtcagact gtagttctat catgcttcct acattagaag 151860 gaggaacagt tttaaagtct cttggtttta atctattacc gttaggttttc atgaaatcct 151920 ttgttttatc cacttcacat tttaaataaa tgtccactat acattctttt gttaatttta 151980 ctagatcgtc atgggtcata gaatttatag gttccgtagt ccatggatcc aaactagcaa 152040 acttcgcgta tacggtatcg cgattagtgt atacaccaac tgtatgaaaa ttaagaaaac 152100 agtttaataa atcaacagaa atatttaatc ctccgtttga tacagatgcg ccatatttat 152160 ggatttcgga ttcacacgtt gtttgtctga ggtgttcgtc tagtgttgct tctacgtaaa 152220 cttcgattcc catatattct ttattgtcag aatcgcatac cgatttatca tcatacactg 152280 tttgaaaact aaatggtata cacatcaaaa taataaataa taacgagtac attctgcaat 152340 attgttatcg taattggaaa attagtgttc gagtgagtcg gattatgtga gtactggatt 152400 gtatatttta ttttatattt tgtaataaga ataaaatgct aatgtcaagt ttattccaat 152460 agatgtctta ttaaaaaaca tatataataa ataacaatgg ctgaatggca taaaattatc 152520 gaggatatct caaaaaataa taagttcgag gatgccgcca tcgttgatta caagactaca 152580 aagaatgttc tagctgctat tcctaacaga acatttgcca agattaatcc tctcatcact 152640 aatcgtaata ttctaaaacc tcttattggt cagaaatatt gtattgtata tactaactct 152700 ctaatggatg agaacacgta tgctatggag ttgcttactg ggtacgcccc tgtatctccg 152760 atcgttatag cgagaactca taccgcactt atatttttga tgggtaagcc aacaacatcc 152820 agacgtgacg tgtatagaac gtgtagagat cacgctaccc gtgtacgcgc aactggtaat 152880 taaaataaaa agtaatattc atatgtagta tcaattttaa atgatgatga tgaaatggat 152940 aatatccata ttgacgatgt caataatgcc ggtattggca tacagttcat cgatttttag 153000 atttcattca gaggatgtgg aattatgtta tgggcatttg tattttgata ggatctataa 153060 tgtagtaaat ataaaatata atccgcatat tccatataga tataatttta ttaatcgcac 153120 gttaaccgta gatgaactag acgataatgt cttttttaca catggttat ttttaaaaca 153180 caaatatggt tcacttaatc ctagtttgat tgtctcatta tcaggaaact taaaatataa 153240 tgatatacaa tgctcagtaa atgtatcgtg tctcattaaa aatttggcaa cgagtacatc 153300 tactatatta acatctaaac ataagactta ttctctacat cggtccacgt gtattactat 153360 aataggatac gattctatta tatggtataa agatataaat gacaagtata atgacatcta 153420 tgatttact gcaatatgta tgctaatagc gtctacattg atagtgacca tatacgtgtt 153480 taaaaaaata aaaatgaact cttaattatg ctatgctatt agaaatggat aaaatcaaaa 153540 ttacggttga ttcaaaaatt ggtaatgttg ttaccatatc gtataacttg gaaaagataa 153600 ctattgatgt tacacctaaa aagaaaaaag aaaaggatgt attattagcg caatcagttg 153660 ctgtcgaaga ggcaaaagat gtcaaggtag aagaaaaaaa tattatcgat attgaagatg 153720 acgatgatat ggatgtagaa agcgcataat acgatctata aaaataagta tataaatact 153780 ttttatttac tgtactctta ctgtgtagtg gtgataccct actcgattat ttttttaaaa 153840 aaatacttat tctgattctt ctagccattt ccgtgttcgt tcgaatgcca catcgacgtt 153900 aaagataggg gagtagttga aatctagttc tgcattgttg gtacgcacct caaatgtagt 153960 gttggatatc ttcaacgtat agttgttgag tagtgatggt tttctaaata gaattctctt 154020 catatcattc ttgcacgcgt acatttttag catccatctt ggaattctag atccttgttc 154080 tattcccaat ggtttcatca atagaagatt aaacatatcg tacgaacacg atggagagta 154140 atcgtagcaa aagtaagcat ttcctttaat ctcagatccc ggatactgga tatattttgc 154200 agccaacacg tgcatccatg caacatttcc tacatatacc cggctatgca ccgcgtcatc 154260 atcgactgta cgatacataa tgttaccgtg ttgcttacat tgctcgtaaa agactttcgt 154320 caatttgtct ccttctccgt aaattccagt gggtcttagg caacaagtat acaattttgc 154380 tccattcatg attacggaat tattggcttt cataaccagt tgctcggcca tacgtttaact 154440 tttgcgtat acatgtcctg gtgatatatc ataaagggta tgctcatggc cgatgaatgg 154500 atcaccgtgt ttatttggtc ctattgcttc catgctacta gtatagatca aatacttgat 154560 tcctaggtcc acacaagctg ccaatatagt ctgtgttcca taatagttta ctttcatgat 154620 ttcattatcg gtgtattttc caaatacatc cactagagca gccgtatgaa taatcagatt 154680 taccccatct agcgcttctc tcaccttatc aaagtcgttt atatcacatt gtatatagtt 154740 tataacctta actttcgagg ttattggttg tggatcttct acaatatcta tgactctgat 154800 ttcttgaaca tcatctgcac taattaacag ttttactata tacctgccta gaaatccggc 154860 accaccagta accgcgtaca cggccattgc tgccactcat aatatcagac tacttattct 154920 attttactaa ataatggctg tttgtataat agaccacgat aatatcagag gagttattta 154980 ctttgaacca gtccatggaa aagataaagt tttaggatca gttattggat taaaatccgg 155040 aacgtatagt ttgataattc atcgttacgg agatattagt caaggatgtg attccatagg 155100 cagtccagaa atatttacg gtaacatctt tgtaaacaga tatggtgtag catatgttta 155160 tttagataca gatgtaaata tatctacaat tattggaaag gcgttatcta tttcaaaaaa 155220 tgatcagaga ttagcgtgtg gagtattgg tatttcttac ataaatgaaa agataataca 155280 ttttcttaca attaacgaga atggcgtttg atatatcagt taatgcgtct aaaacaataa 155340 atgcattagt ttacttttct actcagcaaa ataaattagt catacgtaat gaagttaatg 155400 atacacacta cactgtcgaa tttgataggg acaaagtagt tgacacgttt atttcatata 155460 atagacataa tgacaccata gagataagag gggtgcttcc agaggaaact aatattggtt 155520 gcgcggttaa tacgccggtt agtatgactt acttgtataa taagtatagt tttaaactga 155580 ttttagcaga atatataaga cacagaaata ctatatccgg caatatttat tcggcattga 155640 tgacactaga tgatttggct attaaacagt atggagacat tgatctatta tttaatgaga 155700 aacttaaagt agactccgat tcgggactat ttgactttgt caactttgta aaggatatga 155760 tatgttgtga ttctagaata gtagtagctc tatctagtct agtatctaaa cattgggaat 155820 tgacaaataa aaagtatagg tgtatggcat tagccgaaca tatatctgat agtattccaa 155880 tatctgagct atctagacta cgatacaatc tatgtaagta tctacgcggg cacactgaga 155940 gcatagagga tgaatttgat tattttgaag acgatgattc gtctacatgt tctgccgtaa 156000 ccgacaggga aacggatgta taattttttt tatagcgtga aggatatgat aaaaaatata 156060 attgttgtat ttatcccatt ccaatcacct tatatgattc tgtaaaaaaa ttatactgta 156120 acacaatgaa ggaggtcttat agatgtatag aggtcagata ctggtttgat aaactgttta 156180 ttccacataa gtatgtttga ctttatggtt agacccgcat actttaacaa atcactgaaa 156240 attggagtta ggtattgacc tctcagaatc agttgccgtt ctggaacatt aaatgtattt 156300 tttatgatat actccaacgc atttatgtgg gcatacaaca agtcattact aatggagtat 156360 tccaagagaa gagatttcaa cagactgttt atgaactcga atgccgcctc attgtcgctt 156420 atattgatga tgtcgaattc tcccaatatc atcaccgatg agtagctcat cttgttatcg 156480 ggatccaagt tttctaaaga tgtcattaaa ccctcgatca tgaatggatt tatcatcatc 156540 gtttttatgt tggacatgag cttagtccgt ttgtccacat ctatagacga cgatttctga 156600 attatttcat atatccctct ctttaactcc aggaacttgt caggatggtc tactttaata 156660 tgttctcgtc taagagatga aaatctttgg atggttgcac gcgacttttc tctaaaggat 156720 gacgttgccc aagatcctct cttaaatgaa tccatcttat ccttggacaa gatggacagt 156780 ctattttcct tagatggttt aatatttttg ttacccatga tctataaagg tagacctaat 156840 cgtctcggat gaccatatat ttattttcag ttttattata cgcataaatt gtaaaaaata 156900 tgttaggttt acaaaaatgt ctcgtggggc attaatcgtt tttgaaggat tggacaaatc 156960 tggaaaaaca acacaatgta tgaacatcat ggaatcaata ccttcaaaca caataaaata 157020 ccttaacttt cctcagagat ccactgtcac tggaaagatg atagatgact atctaactcg 157080 taaaaaaacc tataatgatc atatagttaa tctattattt tgtgcaaata gatgggagtt 157140 tgcatctttt atacaagaac aactagaaca gggaattact ttaatagttg atagatacgc 157200 atttctgga gtagcgtatg ccgccgctaa aggcgcgtca atgactctca gtaagagtta 157260 tgaatctgga ttgcctaaac ccgacttagt tatattcttg gaatctggta gcaaagaaat 157320 taatagaaac gtcggcgagg aaatttatga agatgttaca ttccaacaaa aggtattaca 157380 agaatataaa aaaatgattg aagaaggaga tattcattgg caaattattt cttctgaatt 157440 cgaggaagat gtaaagaagg agttgattaa gaatatagtt atagaggcta tacacacggt 157500 tactggacca gtggggcaac tgtggatgta atagtgaaat tacatttttt ataaatagat 157560 gttagtacag tgttataaat ggatgaagca tattactctg gcaacttgga atcagtactc 157620 ggatacgtgt ccgatatgca taccgaactc gcatcaatat ctcaattagt tattgccaag 157680 atagaaacta tagataatga tatattaaac aaggacattg taaattttat catgtgtaga 157740 tcaaacttgg ataatccatt tatctctttc ctagatactg tatatactat tatagatcaa 157800 gagatctatc agactgagtt gattaattca ttagacgaca atgaaattat cgattgtata 157860 gttaataagt ttatgagctt ttataaggat aacctagaaa atatagtaga tgctatcatc 157920 actctaaaat atataatgaa taatccagat tttaaaacta cgtatgcaga agtactcggt 157980 tccagaatag cggatataga tattaaacaa gtgatacgtg agaatatact acaattgtct 158040 aatgatatcc gcgaacgata tttgtgaaaa atattaaaaa aaaatacttt ttttattaaa 158100 tgacgtcgct tcgcgaattt agaaaattat gctgtgatat atatcacgca tcaggatata 158160 aagaaaaatc taaattaatt agagacttta taacagatag ggatgataaa tatttgatca 158220 ttaagctatt gcttcccgga ttagacgata gaatttataa catgaacgat aaacaaatta 158280 taaaattata tagtataata tttaaacaat ctcaggaaga tatgctacaa gatttaggat 158340 acggatatat aggagacact attaggactt tcttcaaaga gaacacagaa atccgtccac 158400 gagataaaag cattttaact ttagaagaag tggatagttt tttaactacg ttatcatccg 158460 taactaaaga atcgcatcaa ataaaattat tgactgatat cgcatccgtt tgtacatgta 158520 atgatttaaa atgtgtagtc atgcttattg ataaagatct aaaaattaaa gcgggccctc 158580 ggtacgtact taacgctatt agtcctcatg cctatgatgt gtttagaaaa tctaataact 158640 tgaaagagat aatagaaaat gcatctaaac aaaatctaga ctctatatct atttctgtta 158700 tgactccaat taatcccatg ttagcggaat cgtgtgattc tgtcaataag gcgtttaaaa 158760 aatttccatc aggaatgttt gcggaagtca aatacgatgg tgaaagagta caagttcata 158820 aaaataataa cgagtttgcc ttctttagta gaaacatgaa accagtactc tctcataaag 158880 tggattatct caaagaatac ataccgaaag catttaaaaa agctacgtct atcgtattgg 158940 attctgaaat tgttcttgta gacgaacata atgtaccgct cccgtttgga agtttaggta 159000 tacacaaaaa gaaagaatat aaaaactcta acatgtgttt gttcgtgttt gactgtttgt 159060 actttgatgg attcgatatg acggacattc cattgtacga acgaagatct tttctcaaag 159120 atgttatggt tgaaataccc aatagaatag tattctcaga gttgacgaat attagtaacg 159180 agtctcagtt aactgacgta ttggatgatg cactaacgag aaaattagaa ggattggtct 159240 taaaagatat taatggagta tacgaaccgg gaaagagaag atggttaaaa ataaagcgag 159300 actatttgaa cgagggttcc atggcagatt ctgccgattt agtagtacta ggtgcttact 159360 atggtaaagg agcaaagggt ggtatcatgg cagtctttct aatgggttgt tacgacgatg 159420 aatccggtaa atggaagacg gttaccaagt gttcaggaca cgatgataat acgttaaggg 159480 agttgcaaga ccaattaaag atgattaaaa ttaacaagga tcccaaaaaa attccagagt 159540 ggttagtagt taataaaatc tatattcccg attttgtagt agaggatcca aaacaatctc 159600 agatatggga aatttcagga gcagagttta catcttccaa gtcccatacc gcaaatggaa 159660 tatccattag atttcctaga tttactagga taagagagga taaaacgtgg aaagaatcta 159720 ctcatctaaa cgatttagta aacttgacta aatcttaata gttacataca aattaaaata 159780 acactattta gttggtggtc gccatggatg gtgtattgt atactgtcta aacgcgttag 159840 taaaacatgg cgaggaaata aatcatataa aaaatgattt catgattaaa ccatgttgtg 159900 aaaaagtcaa gaacgttcac attggcggac aatctaaaaa caatacagtg attgcagatt 159960 tgccatatat ggataatgcg gtatccgatg tatgcaattc actgtataaa aagaatgtat 160020 caagaatatc cagatttgct aatttgataa agatagatga cgatgacaag actcctactg 160080 gtgtatataa ttattttaaa cctaaagatg ccattcctgt tattatatcc ataggaaagg 160140 atagagatgt ttgtgaacta ttaatctcat ctgataaagc gtgtgcgtgt atagagttaa 160200 attcatataa agtagccatt cttcccatgg atgtttcctt ttttaccaaa ggaaatgcat 160260 cattgattat tctcctgttt gatttctcta tcgatgcggc acctctctta agaagtgtaa 160320 ccgataataa tgttattata tctagacacc agcgtctaca tgacgagctt ccgagttcca 160380 attggttcaa gttttacata agtataaagt ccgactattg ttctatatta tatatggttg 160440 ttgatggatc tgtgatgcat gcaatagctg ataatagaac ttacgcaaat attagcaaaa 160500 atatattaga caatactaca attaacgatg agtgtagatg ctgttatttt gaaccacaga 160560 ttaggattct tgatagagat gagatgctca atggatcatc gtgtgatatg aacagacatt 160620 gtattatgat gaatttacct gatgtaggcg aatttggatc tagtatgttg gggaaatatg 160680 aacctgacat gattaagatt gctctttcgg tggctggtat ttggaaagtt ttataggtag 160740 ttgatagaac aaaatacata attttgtaaa aataaatcac tttttatact aatatgacac 160800 gattaccaat acttttgtta ctaatatcat tagtatacgc tacacctttt cctcagacat 160860 ctaaaaaaat aggtgatgat gcaactttat catgtaatcg aaataataca aatgactacg 160920 ttgttatgag tgcttggtat aaggagccca attccattat tcttttagct gctaaaagcg 160980 acgtcttgta ttttgataat tataccaagg ataaaatatc ttacgactct ccatacgatg 161040 atctagttac aactatcaca attaaatcat tgactgctag agatgccggt acttatgtat 161100 gtgcattctt tatgacatcg cctacaaatg acactgataa agtagattat gaagaatact 161160 ccacagagtt gattgtaaat acagatagtg aatcgactat agacataata ctatctggat 161220 ctacacattc accggaaact agttctgaga aacctgatta tatagataat tctaattgct 161280 cgtcggtatt cgaaatcgcg actccggaac caattactga taatgtagaa gatcatacag 161340 acaccgtcac atacactagt gatagcatta atacagtaag tgcatcatct ggagaatcca 161400 caacagacga gactccggaa ccaattactg ataaagaaga agatcataca gttacagaca 161460 ctgtctcata cactacagta agtacatcat ctggaattgt cactactaaa tcaaccaccg 161520 atgatgcgga tctttatgat acgtacaatg ataatgatac agtaccatca actactgtag 161580 gcggtagtac aacctctatt agcaattata aaaccaagga ctttgtagaa atatttggta 161640 ttaccgcatt aattatattg tcggccgtgg caatattctg tattacatat tatatatata 161700 ataaacgttc acgtaaatac aaaacagaga acaaagtcta gatttttgac ttacataaat 161760 gtctgggata gtaaaatcta tcatattgag cgggccatct ggtttaggaa agacagccat 161820 agccaaaaga ctatgggaat atatttggat ttgtggtgtc ccataccact agatttcctc 161880 gtcctatgga acgagaaggt gtcgattacc attacgttaa cagagaggcc atctggaagg 161940 gaatagccgc cggaacatac tgagttttta ggaaatattt acggaacttc taaaactgct 162000 gtgaatacag cggctattaa taatcgtatt tgtgtgatgg atctaaacat cgacggtgtt 162060 agaagtttta aaaatactta cctaatgcct tactcggtgt atataagacc tacctctctt 162120 aaaatggttg agaccaagct tcgttgtaga aacactgaag cggatgatga gattcatcgt 162180 cgtgtgatgt tggcaaaaac tgacatggat gaggcaggtg aagccggtct attcgacact 162240 attatcattg aagatgatgt gaatttagca tatagtaagt taattcagat actacaggac 162300 cgtattagaa tgtattttaa cactaattag agacttaaga cttaaaactt gataattaat 162360 aatataactc gtttttatat gtggctattt caacgtctaa tgtattagtt aaatattaaa 162420 acttaccacg taaaacttaa aatttaaaat gatatttcat tgacagatag atcacacatt 162480 atgaactttc aaggacttgt gttaactgac aattgcaaaa atcaatgggt cgttggacca 162540 ttaatagggaa aaggtggatt tggtagtatt tatactacta atgacaataa ttatgtagta 162600 aaaatagagc ccaaagctaa cggatcatta tttaccgaac aggcatttta tactagagta 162660 cttaaaccat ccgttatcga agaatggaaa aaatctcaca atataaagca cgtaggtctt 162720 atcacgtgca aggcatttgg tctatacaaa tccattaatg tggaatatcg attcttggta 162780 attaatagat taggtgcaga tctagatgcg gtgatcagag ccaataataa tagattacca 162840 aaaaggtcgg tgatgttgat cggaatcgaa atcttaaata ccatacaatt tatgcacgag 162900 caaggatatt ctcacggaga tattaaagcg agtaatatag tcttggatca aatagataag 162960 aataaattat atctagtgga ttacggattg gtttctaaat tcatgtctaa tggcgaacat 163020 gttccattta taagaaatcc aaataaaatg gataacggta ctctagaatt tacacctata 163080 gattcgcata aaggatacgt tgtatctaga cgtggagatc tagaaacact tggatattgt 163140 atgattagat ggttgggagg tatcttgcca tggactaaga tatctgaaac aaagaattgt 163200 gcattagtaa gtgccacaaa acagaaatat gttaacaata ctgcgacttt gttaatgacc 163260 agtttgcaat atgcacctag agaattgctg caatatatta ccatggtaaa ctctttgaca 163320 tattttgagg aacccaatta cgacaagttt cggcacatat taatgcaggg tgtatattat 163380 taagtgtggt gtttggttga tgtaaaattt ttgtcgataa aaattaaaaa ataacttaat 163440 ttattattga tctcgtgtgt acaaccgaaa tcatggcgat gttttacgca cacgctctcg 163500 gtgggtacga cgagaatctt catgcctttc ctggaatatc atcgactgtt gccaatgatg 163560 tcagtttata ataacaagta tgacattgta aaagacaaat atatgtggtg ttacagtcag 163620 gtgaacaaga gatatattgg agcactgctg cctatgtttg agtgcaatga atatctacaa 163680 attggagatc cgatccatga tcaagaagga aatcacatat cgccacaaaa actactatgc 163740 tctaagcgga atcgggtacg agagtctaga cttgtgtttg gaaggagtag ggattcatca 163800 tcacgtactt gaaacagaaa acgctgtata tggaaaagtt caacatgatt attctactat 163860 caaagagaag gccaaagaaa tgaatgcact cagttcagga cctatcatcg attaccacgt 163920 ctggatagga gattgtatct gtcaagttac tgctgtggac gtacatggaa aggaaattat 163980 gagaatgaga ttcaaaaagg gtgcggtgct tccgatccca aatctggtaa aagttaaact 164040 tggggagaat gatacagaaa atctttcttc tactatatcg gcggcaccat cgaggtaacc 164100 acctctctgg aagacagtgt gaatcatgta ctcatgaaac gtttggaatc tatacgccat 164160 atgtggtctg ttgtatatga tcattttgat attgtgaatg gtaaagaatg ctgttatgtg 164220 catacgcatt tgtctaatca aaatcttata ccgagtactg taaaaacaaa tttgtacatg 164280 aagactatgg gatcatgcat tcaaatgagt atcttagcga actgaaggaa tcaggtggat 164340 ggaggtcccag accagaaatg caggaatttg aatatccaga tggagtggaa gacactgaat 164400 caattgagag attggtagag gagttcttca atagatcaga acttcaggct ggtaaatcta 164460 ttaatgttaa acatacatct gtttcagcta agcaactaag aacacgtata ctctcatctt 164520 ttgccaacac agagggtgga tatttgttca ttggagttga taataataca cacaaagtat 164580 ttggattcac ggtgggttac gactacctca gactgataga gaatgatata gaaaagcata 164640 tcaaaagact ttgtgttgtg tatttctgtg agaagaaaga ggacatcaag tacacgtgtc 164700 gattcatcaa gtggggatga ggctacctcg acatacgtgt gcgctatcaa agtggaaaga 164760 tgctgttgtg ctgtgtttgc agattggcca gaatcatggt atcaagaagt attctccaga 164820 tgaataggtg tcacatataa aattttaatt aatgtaacta tagagaacaa ataataggtt 164880 gtaatatcat atagacaata actaacaatt aattagtaac tgttatctct ttttaactaa 164940 ctaactatac ctattaatac atcgtaatta tagttcttaa catctattaa tcattgattc 165000 gcttctttaa ttttttataa accaacattg ttaattgaaa aggtataaca tgttacagaa 165060 tataaattat atatggattt tttttaaaaa ggaaatactt gactggagtg tatatttatc 165120 tcttcattat ataacacgcg tgttttccaa tttttccaca tcccatataa tacaggatta 165180 taatctcgtt cgaacatacg agaaagtgga taaaacaata gttgattttt tatctaggtt 165240 gccaaattta ttccatattt tagaatatgg ggaaaatatt ctacatattt attctatgga 165300 tgatgctaat acgaatatta taattttttt tctagataga gtattaaata ttaataagaa 165360 cgggtcattt atacacaatc tcaggttatc atcatccatt aatataaaag aatatgtata 165420 tcaattagtt aataatgatc atccagataa taggataaga ctaatgcttg aaaatggacg 165480 tagaacaaga cattttttgt cctatatatc agatacagtt aatatctata tatgtatttt 165540 atatagatgc cgaagacagt tacggttgta cattattaca tagatgtata tatcactata 165600 agaaatcaga atcagaatca gaatcataca atgaattaat taagatattg ttaaataatg 165660 gatcagatgt agataaaaaa gatacgtacg gaaacacacc ttttatccta ttatgtaaac 165720 acgatatcaa caacgtgggaa ttgtttgaga tatgtttaga gaatgctaat atagactctg 165780 tagactttaa tagatataca cctcttcatt atgtctcatg tcgtaataaa tatgattttg 165840 taaagttat aatttctaaa ggagcaaatg ttaatgcgcg taataaattc ggaactactc 165900 cattttatg tggaattata cacggtatct cgcttataaa actatatttg gaatcagaca 165960 cagagttaga aatagataat gaacatatag ttcgtcattt aataattttt gatgctgttg 166020 aatctttaga ttatctatta tccagaggag ttattgatat taactatcgt actatttacg 166080 acgctgtcag ttataatgcg tataatacgt tggtctatct attaaacaga aatggtgatt 166140 ttgagacgat tactactagt ggatgtacat gtatttcgga agcagtcgca aacaacaaca 166200 aaataataat ggaagtacta ttgtctaaac gaccatcttt gaaaattatg atacagtcta 166260 tgatagcaat tactaaacat aaacagcata atgcagattt attgaaaatg tgtataaaat 166320 atactgcgtg tatgaccgat tatgatactc ttatagatgt acaatcacta cagcaatata 166380 aatggtatat tttaagatgt ttcgatgaaa tagatatcat gaagagatgt tatataaaaa 166440 ataaaactgt attccaatta gttttttgta tcaaagacat taatacttta atgagatacg 166500 gtaaacatcc ttctttcgtg aagtgcacta gtctcgacgt atacggaagt cgtgtacgta 166560 atatcatagc atctattaga tatcgtcaga gattaattag tctattatcc aagaagctgg 166620 atcctggaga taaatggtcg tgttttccta acgaaataaa atataacgat aacgaactgt 166680 ccacatatct aaaaatctta taaacactat taaaatataa aatcacacta catcattgtt 166740 tccttttagt gctcgacagt gtatactatt tttaacgctc ataaataaaa atgaaaacga 166800 tttccgttgt tacgttgtta tgcgtactac ctgctgttgt ttattcaaca tgtactgtac 166860 ccactatgaa taacgctaaa ttaacgtcta ccgaaacatc gtttaataat aaccagaaag 166920 ttacgtttac atgtgatcag ggatatcatt cttcggatcc aaatgctgtc tgcgaaacag 166980 ataaatggaa atacgaaaat ccatgcaaaa aaatgtgcac agtttctgat tacatctctg 167040 aactatataa taaaccgcta tacgaagtga attccaccat gacactaagt tgcaacggcg 167100 aaacaaaata ttttcgttgc gaagaaaaaa atggaaatac ttcttggaat gatactgtta 167160 cgtgtcctaa tgcggaatgt caacctcttc aattagaaca cggatcgtgt caaccagtta 167220 aagaaaaata ctcatttggg gaatatatga ctatcaactg tgatgttgga tatgaggtta 167280 ttggtgcttc gtacataagt tgtacagcta attcttggaa tgttattcca tcatgtcaac 167340 aaaaatgtga tatgccgtct ctatctaacg gattaatttc cggatctaca ttttctatcg 167400 gtggcgttat acatcttagt tgtaaaagtg gttttacact aacggggtct ccatcatcca 167460 catgtatcga cggtaaatgg aatcccgtac tcccaacatg tgtacgatct aacgaaaaat 167520 ttgatccagt ggatgatggt cccgacgatg agacagattt gagcaaactc tcgaaagacg 167580 ttgtacaata tgaacaagaa atagaatcgt tagaagcaac ttatcatata atcatagtgg 167640 cgttaacaat tatgggcgtc atatttttaa tctccgttat agtatagtt tgttcctgtg 167700 acaaaaataa tgaccaatat aagttccata aattgctacc gtgaatataa atccgttaaa 167760 ataattaata atttaataac aaacaagtat caaaagatta aagacttata gctagaatca 167820 attgagatgt cttcttcagt ggatgttgat atctacgatg ccgttagagc atttttactc 167880 aggcactatt ataacaagag atttattgtg tatggaagaa gtaacgccat attacataat 167940 atatacaggc tatttacaag atgcgccgtt ataccgttcg atgatatagt acgtactatg 168000 ccaaatgaat cacgtgttaa acaatgggtg atggatacac ttaatggtat aatgatgaat 168060 gaacgcgatg tttctgtaag cgttggcacc ggaatactat tcatggaaat gtttttcgat 168120 tacaataaaa atagtatcaa caatcaacta atgtatgata taattaatag cgtatctata 168180 attctagcta atgagagata tagaagcgct tttaacgacg atggtatata catccgtaga 168240 aatatgatta acaagttgta cggatacgca tctctaacta ctattggcac gatcgctgga 168300 ggtgtttgtt attatctgtt gatgcatcta gttagtttgt ataaataatt atttcaatat 168360 actagttaaa attttaagat tttaaatgta taaaaaacta ataacgtttt tatttgtaat 168420 aggtgcatta gcatcctatt cgaataatga gtacactccg tttaataaac tgagtgtaaa 168480 actctatata gatggagtag ataatataga aaattcatat actgatgata ataatgaatt 168540 ggtgttaaat tttaaagagt acacaatttc tattattaca gagtcatgcg acgtcggatt 168600 tgattccata gatatagatg ttataaacga ctataaaatt attgatatgt ataccattga 168660 ctcgtctact attcaacgca gaggtcacac gtgtagaata tctaccaaat tatcatgcca 168720 ttatgataag tacccttata ttcacaaata tgatggtgat gagcgacaat attctattac 168780 tgcagaggga aaatgctata aaggaataaa atatgaaata agtatgatca acgatgatac 168840 tctattgaga aaacatactc ttaaaattgg atctacttat atatttgatc gtcatggaca 168900 tagtaataca tattattcaa aatatgattt ttaaaaattt aaaatatatt atcacttcag 168960 tgacagtagt caaataacaa acaacaccat gagatatatt ataattctcg cagttttgtt 169020 cattaatagt atacatgcta aaataactag ttataagttt gaatccgtca attttgattc 169080 caaaattgaa tggactgggg atggtctata caatatatcc cttaaaaatt atggcatcaa 169140 gacgtggcaa acaatgtata caaatgtacc agaaggaaca tacgacatat ccgcatttcc 169200 aaagaatgat ttcgtatctt tctgggttaa atttgaacaa ggcgattata aagtggaaga 169260 gtattgtacg ggactatgcg tcgaagtaaa aattggacca ccgactgtaa cattaactga 169320 atacgacgac catatcaatt tgtacatcga gcatccgtat gctactagag gtagcaaaaa 169380 gattcctatt tacaaacgcg gtgacatgtg tgatatctac ttgttgtata cggctaactt 169440 cacattcgga gattctaaag aaccagtacc atatgatatc gatgactacg attgcacgtc 169500 tacaggttgc agcatagact ttgtcacaac agaaaaagtg tgcgtgacag cacagggagc 169560 cacagaaggg tttctcgaaa aaattactcc atggagttcg aaagtatgtc tgacacctaa 169620 aaagagtgta tatacatgcg caattagatc caaagaagat gttcccaatt tcaaggacaa 169680 aatggccaga gttatcaaga gaaaatttaa tacacagtct caatcttatt taactaaatt 169740 tctcggtagc acatcaaatg atgttaccac ttttcttagc atgcttaact tgactaaata 169800 ttcataacta atttttatta atgatacaaa aacgaaataa aactgcatat tatacactgg 169860 ttaacgccct tataggctct aaccattttc aagatgaggt ccctgattat agtccttctg 169920 ttcccctcta tcatctactc catgtctatt agacgatgtg agaagactga agaggaaaca 169980 tggggattga aaatagggtt gtgtataatt gccaaagatt tctatcccga aagaactgat 170040 tgcagtgttc atctcccaac tgcaagtgaa ggattgataa ctgaaggcaa tggattcagg 170100 gatatacgaa acaccgataa attataaaaa aagcaatgtg tccgctgttt ccgttaataa 170160 tactattttc gtaactggcg gattattcat aaataactct aatagcacga tcgtggttaa 170220 caatatgggaa aaacttgaca tttataaaga caaacaatgg tcgattatag aaatgcctat 170280 ggctagggta tatcacggca tcgactcgac atttggaatg ttatattttg ccggaggtct 170340 atccgttacc gaacaatatg gtaatttaga gaaaaacaac gagatatctt gttacaatcc 170400 tagaacgaat aagtggtttg atatttcata tactatttat aagatatcca tatcatcatt 170460 gtgtaaacta aataacgtct tctatgtatt tagtaaggac attggatatg tggaaaagta 170520 tgatggtctc cccgctataa aggcattatc aacttctcct tattgattga aaatgaaaat 170580 ataaatagtt tttatgtata gcagtattac cctatagttt tattgcttac tactaacatg 170640 gatacagatg ttacaaatgt agaagatatc ataaatgaaa tagatagaga gaaagaagaa 170700 atactaaaaa atgtagaaat tgaaaataat aaaaacatta acaagaatca tccaagtgga 170760 tatattagag aagcactcgt tattaatacc agtagtaata gtgattccat tgataaagaa 170820 gttatagaat gtatcagtca cgatgtagga atatagatca tatctactaa tttttataat 170880 cgatacaaaa cataaaaaac aactcgttat tacatagcag gcatggaatc cttcaagtat 170940 tgttttgata acgatggcaa gaaatggatt atcggaaata ctttatattc tggtaattca 171000 atactctata aggtcagaaa aaatttcact agttcgttct acaattacgt aatgaagata 171060 gatcacaaat cacacaagcc attgttgtct gaaatacgat tctatatatc tgtattggat 171120 cctttgacta tcgacaactg gacacgggaa cgtggtataa agtatttggc tattccagat 171180 ctgtatggaa ttggagaaac cgatgattat atgttcttcg ttataaagaa ttcgggaaga 171240 gtattcgccc caaaggatac tgaatcagtc ttcgaagcat gcgtcactat gataaacacg 171300 ttagagttta tacactctca aggatttacc catggaaaaa tagaaccgag gaatatactg 171360 attagaaata aacgtctttc actaattgac tattctagaa ctaacaaact atacaagagt 171420 ggaaactcac atatagatta caacgaggac atgataactt caggaaatat caattatatg 171480 tggttagaca atcatcttgg agcaacagtt tcaagacgag gagattaga aatgttggga 171540 tattgcatga tagaatggtt cggtggcaaa cttccatgga aaaacgaaag tagtataaaa 171600 gtaataaaac aaaaaaaaga atataaaaaa tttatagcta ctttctttga ggactgtttt 171660 cctgaaggaa atgaacctct ggaattagtt agatatatag aattagtata cacgttagat 171720 tattctcaaa ctcctaatta tgacagacta cgtaaactgt ttatacaaga ttgaaattat 171780 attctttttt ttatagagtg tggtagtgtt acggatattt aatattagac tatctctatc 171840 gcgctacacg accaatatcg attactatgg atatcttcta tgaaaggaga gaatgtattc 171900 atttctccag cgtcaatctc gtcagtattg acaatactgt attatggagc taatggatcc 171960 actgctgaac agctatcgaa atatgtagaa acggaggaga acacggataa ggttagcgct 172020 caaaatatct cattcaaatc cataaataaa gtatatgggc gatattctgc cgtgtttaaa 172080 gattcctttt tgagaaaaat tggcgataag tttcaaactg ttgacttcac tgattgtcgc 172140 actatagatg caatcaacaa gtgtgtagat atctttactg aggggaaaat caatccacta 172200 ttggatgaac cattgtctcc tagcaattag tgccgtatac tttaaagcaa aatggttgac 172260 gccattcgaa aaggaattta ccagtgatta tcccttttac gtatcaccaa cggaaatggt 172320 agacgtaagt atgatgtcta tgtacggcga gctatttaat cacgcatctg taaaagaatc 172380 attcggcaac ttttcaatca tagaactgcc atatgttgga gatactagta tgatggtcat 172440 tcttccagac aagattgatg gattagaatc catagaacaa aatctaacag atacaaattt 172500 taagaaatgg tgtgacttta tggatgctat gtttatagat gttcacattc ccaagtttaa 172560 ggtaacaggt tcgtataatc ttgtggatac tctagtaaag ttgggactga cagaggtgtt 172620 ctattcaact ggcgattata gcaatatgtg taattcagat gtgagtgtcg acgctatgat 172680 ccacaaaacg tatatagatg tcaatgaaga gtatacagaa gcagctgcag caacttctgt 172740 actagtggca gactgtgcat caacagttac aaatgagttc tgtgcagatc atccgttcat 172800 ctatgtgatt aggcatgttg atggcaaaat tcttttcgtt ggtagatatt gctctccaac 172860 aactaattgt taaccatttt ttttaaaaaa aatagaaaaa acatgtggta ttagtgcagg 172920 tcgttgttct tccaattgca attggtaaga tgacggccaa ctttagtacc cacgtctttt 172980 caccacagca ctgtggatgt gacagactga ccagtattga tgacgtcaaa caatgtttga 173040 ctgaatatat ttattggtcg tcctatgcat accgcaacag gcaatgcgct ggacaattgt 173100 attccacact cctctctttt agagatgatg cggaattagt gttcatcgac attcgcgagc 173160 tggtaaaaaa tatgccgtgg gatgatgtca aagattgtac agaaatcatc cgttgttata 173220 taccggatga gcaaaaaacc atcagagaga tttcggccat catcggactt tgtgcatatg 173280 ctgctactta ctggggaggt gaagaccatc ccactagtaa cagtctgaac gcattgtttg 173340 tgatgcttga gatgctaaat tacgtggatt ataacatcat attccggcgt atgaattgat 173400 gagttgtaca tcttgacatt ttctttcttc tcttctccct ttcttctctt ctcccttcct 173460 ccctcttctc cctttcccag aaacaaactt ttttacccac tataaaataa aatgagtata 173520 ctacctgtta tatttctttc tatatttttt tattcttcat tcgttcagac ttttaacgcg 173580 cctgaatgta tcgacaaagg gcaatatttt gcatcattca tggagttaga aaacgagcca 173640 gtaatcttac catgtcctca aataaatacg ctatcatccg gatataatat attagatatt 173700 ttatgggaaa aacgaggagc ggataatgat agaattatac cgatagataa tggtagcaat 173760 atgctaattc tgaacccgac acaatcagac tctggtattt atatatgcat taccacgaac 173820 gaaacctact gtgacatgat gtcgttaaat ttgacaatcg tgtctgtctc agaatcaaat 173880 atagatctta tctcgtatcc acaaatagta aatgagagat ctactggcga aatggtatgt 173940 cccaatatta atgcatttat tgctagtaac gtaaacgcag atattatatg gagcggacat 174000 cgacgcctta gaaataagag acttaaacaa cggacacctg gaattattac catagaagat 174060 gttagaaaaa atgatgctgg ttattataca tgtgttttag aatatatata cagaggtaaa 174120 acatataacg taaccagaat tgtaaaatta gaggtacggg ataaaataat accttctact 174180 atgcaattac cagatggcat tgtaacttca ataggtagta atttgactat tgcgtgtaga 174240 gtatcgttga gacctcccac aacggatgca gacgtctttt ggataagtaa tggtatgtat 174300 tacgaagaag atgatgggga cggaaacggt agaataagtg tagcaaataa aatctatatg 174360 accgataaga gacgtgttat tacatcccgg ttaaacatta atcctgtcaa ggaagaagat 174420 gctacaacgt ttacgtgtat ggcgtttact attcctagca tcagcaaaac agttactgtt 174480 agtataacgt gaatgtatgt tgttacattt ccatgtcaat tgagtttata agaattttta 174540 tacattatct tccaacaaac aattgacgaa cgtattgcta tgattaactc ccacgatact 174600 atgcatatta ttaatcatta acttgcagac tatacctagt gctattttga catactcatg 174660 ttcttgtgta attgcggtat ctatattatt aaagtacgta aatctagcta tagtttattatt 174720 atttaatttt agataatata ccgtctcctt atttttaaaa attgccacat cctttattaa 174780 atcatgaatg ggaatttcta tgtcatcgtt agtatattgt gaacaacaag agcagatatc 174840 tataggaaag ggtggaatgc gatacattga tctatgtagt tttaaaacac acgcgaactt 174900 tgaagaattt atataaatca ttccatcgat acatccttct atgttgacat gtatatatcc 174960 aggaattcgt ttattaatat cgggaaatgt ataaactaaa acattgcccg aaagcggtgc 175020 ctctatctgc gttatatccg ttcttaactt acaaaatgta accaatacct ttgcatgact 175080 tgttttgttc ggcaacgtta gtttaaactt gacgaatgga ttaattacaa tagcatgatc 175140 cgcgcatcta ttaagttttt ttactttaac gcccttgtat gtttttacag agactttatc 175200 taaatttcta gtgcttgtat gtgttataaa tataacggga tatagaaccg aatcacctac 175260 cttagatacc caattacatt ttatcagatc cagataataa acaaattttg tcgccctaac 175320 taattctata ttgttatata ttttacaatt ggttatgata tcatgtaata acttggagtc 175380 taacgcgcat cgtcgtacgt ttatacaatt gtgatttagt gtagtatatc tacacatgta 175440 tttttccgca ctatagtatt ctggactagt gataaaacta tcgttatatc tgtcttcaat 175500 gaactcatcg agatattgct ctctgtcata ttcatacacc tgcataaact ttctagacat 175560 cttacaatcc gtgttatttt aggatcatat ttacatattt acgggtatat caaagatgtt 175620 agattagtta atgggaatcg tctataataa tgaatattaa acaattatat gaggactttt 175680 accacaaagc atcataaaaa tgagtcgtcg tctgatttat gttttaaata tcaaccgcga 175740 atcaactcat aaaatacaag agaatgaaat atatacatat tttagtcatt gcaatataga 175800 ccatacttct acagaacttg attttgtagt taaaaactat gatctaaaca gacgacaacc 175860 tgtaactggg tatactgcac tacactgcta tttgtataat aattacttta caaacgatgt 175920 actgaagata ttattaaatc atggagtgga tgtaacgatg aaaaccagta gcggacgtat 175980 gcctgtttat atattgctta ctagatgttg taatatttca catgatgtag tgatagatat 176040 gatagacaaa gataaaaacc acttattaca tagagactat tccaacctac tactagagta 176100 tataaaatct cgttacatgt tattgaagga agaggatatc gatgagaaca tagtatccac 176160 tttattagat aagggaatcg atcctaactt taaacaagac ggatatacag cgttacatta 176220 ttattatttg tgtctcgcac acgtttataa accaggtgag tgtagaaaac cgataacgat 176280 aaaaaaggcc aagcgaatta tttctttgtt tatacaacat ggagctaatc taaacgcgtt 176340 agataattgt ggtaatacac cattccattt gtatcttagt attgaaatgt gtaataatat 176400 tcatatgact aaaatgctgt tgacttttaa tccgaatttc gaaatatgta ataatcatgg 176460 attaacgcct atactatgtt atataacttc cgactacata caacacgata ttcttgttat 176520 gttaatacat cactatgaaa caaatgttgg agaaatgccg atagatgagc gtcgtataat 176580 cgtattcgag tttatcaaaa catattctac acgtccggca gattcgataa cttatttgat 176640 gaataggttt aaaaatataa atatttatac ccgctatgaa ggaaagacat tattacacgt 176700 agcatgtgaa tataataata cacacgtaat agattatctt atacgtatca acggagatat 176760 aaatgcgtta accgacaata acaaacacgc tacacaactc attatagata acaaagaaaa 176820 ttccccatat accattaatt gtttactgta tatacttaga tatattgtag ataagaatgt 176880 gataagatcg ttggtggatc aacttccatc tctacctatc tttcgtcgct tatcatacta 176940 gtcatatcct aaatgttgat catattccac caaatgattg tgaaagagat tgagattaaa 177000 tcgtctaaca aacaattagt ttttatgaca ttaacatata ataaataaat taatcattat 177060 tgacttaacg atgacgaaag ttatcatcat cttaggattc ttgattatta atacaaattc 177120 attgtctatg aaatgtgaac aaggtgtctc atattataat tcacaagaat taaagtgttg 177180 taaactatgt aagccaggaa catattcaga tcatcgatgt gataaataca gcgataccat 177240 ttgtggacat tgtccgagtg acacattcac gtcaatatat aatcgttctc cttggtgtca 177300 tagttgtaga ggtccatgtg gtactaatcg agtagaggtc acaccttgta cacctaccac 177360 aaatagaatc tgtcattgtg actcgaatag ttattgtctc cttaaagctt ctgatggtaa 177420 ctgtgttaca tgtgctccta aaacaaaatg tggtcgtggg tatggaaaga aaggagaaga 177480 tgaaatgggt aataccattt gtaagaaatg tcggaagggt acttattcag atattgtatc 177540 tgactctgat caatgtaaac caatgacaag ataagactta ctcgcatcta ctggatagac 177600 ataaaatatc ctcctcgtaa taatgaaata taatatacac taattattaa tatcaataac 177660 aatcgagtat taatatatag gtcattttta aatccctttt gggttccgtc ccaaacggcg 177720 tttcggtctg cgtcgccgcc atggccatgc cgagcctctc cgcgtgctcc tccatcgagg 177780 acgacttcaa ctatggcagc tcggtggcgt ctgccagcgt gcacatacga atggcatttc 177840 taagaaaagt ctacggtatc ctttgtctac aatttctttt aacaacggca acaactgcag 177900 tatttttata ctttgactgc atgcggacat ttatacaagg gagtcctgtt ctaatattgg 177960 catcaatgtt cggatctata ggcttgattt tcgcattgac tttacacaga cataaacatc 178020 ccctgaatct gtacctgctt tgtggattta cactgtcgga atctctaacg ctggcctctg 178080 ttgttacttt ctatgatgg catgtcgtta tgcaagcttt catgctgact actgcagcgt 178140 ttcttgctct gactacatat actctacaat caaagagaga tttcagtaaa cttggagcag 178200 gattgtttgc tgctttgtgg attttaattt tgtcaggact cttggggata tttgtgcaaa 178260 atgagacagt gaagctggtc ctgtctgctt ttggggccct tgtattctgt ggattcatta 178320 tctatgacac gcactcacta atacataagc tctcgcctga agagtatgtg ttagcctcta 178380 tcaatctcta cttggatatc atcaatctgt tcttgcatct gttgcagctt ttggaagtat 178440 ctaataagaa ataaagttta aaatagaatt aataaaaaca tataggtcat tttttaaaca 178500 tggattgggaa accaaggtag ttagttaata cacacaagat atattttttt cacatcatcc 178560 acccatgggt aacaccaagg ttgttagtta ataatataca agatattttt tctcactctg 178620 atccatgtaa accaaggacg agataagaca ctctcattcc tcatccacaa cccattaaaa 178680 aaatggaaat taaagccctc tattagcata aacggctaca ggtctacctt cacaatggcc 178740 tttccttgtg cccagttcag accctgtcat tgccacgcta ctaaggactc cctgaatacc 178800 gtggccgacg tcagacattg tctgactgaa tacatcctgt gggtttctca tagatggacc 178860 catagagaaa gcgcagggcc tctctacagg cttctcatct ctttcagaac tgatgcaacg 178920 gagctctttg gtggtgagtt gaaggattca cttccgtggg acaattgcgt ggagatcatt 178980 aaatgtttca tcagaaatga ctccatgaaa accgccaaag aacttcgtgc aatcattgga 179040 ctttgtactc aatcagctat cgtctctgga agagtcttca acgataagta tatcgacata 179100 ctacttatgc tgcgaaagat tctgaacgag aacgactatc tcaccctctt ggatcatatc 179160 cgcactgcta aatactaaat ctccttcatg ctctctcact acacttttta tcatcttatg 179220 aggaatgatt gccttcgtga aataggaata attagcacca gaatagctat ggattattgt 179280 ggtagagagt gcactattct atgtcgtcta ctggatgaag atgtgacgta caaaaaaata 179340 aaaccagaga ttgaaacgtg tcacaactta tcaaaacata tagatagacg aggaaacaat 179400 gcgctacatt gttacgtctt caataaatgc gatacagaca ttaagattgt tcggctgtta 179460 ctctctcgcg gagtcgagag actttgtaga aacaacgaag gattaactcc gctaggagca 179520 tacagtaagc atagatacgt caaatctcag attgtgcatc tactgatatc cagctattcg 179580 aattcctcta acgaactcaa gtcgaatata aatgatttcg atctgtattc gtataatatc 179640 gacttacgtc tgctaaaata cctaattgtg gataaacgga tacgtccgtc caagaatacg 179700 aattatgcaa tcaatggtct cggattggtg gatatatacg taacgacgcc taatccgaga 179760 ccagaagtat tgctatggct tcttaaatca gaatgttaca gcaccggtta cgtatttcgt 179820 acctgtatgt acgacagtga tatgtgtaag aactctcttc attactatat atcgtctcat 179880 agagaatctc aatctctatc caaggatgta attaaatgtt tgatcgataa caatgtttcc 179940 atccatggca gagacgaagg aggatcttta cccatccaat actactggtc ttgctcaacc 180000 atagatatag agattgttaa attattatta ataaaggatg tggacacgtg tagagtatac 180060 gacgtcagcc ctatattaga ggcgtattat ctaaacaagc gatttagagt aaccccatat 180120 aatgtagaca tggaaatcgt taatcttctt attgagagac gtcatactct tgtcgacgta 180180 atgcgtagta ttacttcgta cgattccaga gaatataacc actacatcat cgataacatt 180240 ctaaagagat ttagacaaca ggatgtacaa gccatgttga taaactactt acattacggc 180300 gatatggtcg ttcgatgcat gttagataac ggacaacaac tatcctctgc acgactactt 180360 tgttaataat aatctcgtcg atgtaaacgt cgtaaggttt atcgtggaaa atatggacac 180420 gcggctgtaa atcacgtatc gaacaatggc cgtctatgta tgtacggtct gatattatcg 180480 agatttaata attgcgggta tcactgttat gaaaccatac tgatagatgt atttgatata 180540 ctaagcaagt acatggatga tatagatatg atcgataact ctactatatt acgcggtcga 180600 tgtcaataat atacaatttg caaagcggtt attggaatat ggagcgagtg ttacaacatc 180660 acgctcgata atcaatacgg ccatccagaa aagcagttac agaagagaaa acaaaacgag 180720 gatagttgat ttattactga gttaccatcc cactctagag actatgattg acgcatttaa 180780 tagagatata cgctatctat atcctgaacc attattcgcc tgtatcagat acgccttaat 180840 cctagatgat gattttcctt ctaaagtaaa gtatgatatc tccggtcgtc ataaggaact 180900 aaagcgctat agagcagaca ttaatagaat gaagaatgtc tacatatcag gcgtctccat 180960 gtttgatata ttctttaaac gaagcaaacg ccacagactg agatacgcaa agaatccgac 181020 atcaaatggt acaaaaaaga actaacgtcc atcattacag aaactgtaaa gaacaatgag 181080 aggatcgact ccatagtgga caacattaat acagacgata acttgatttc gaaattaccc 181140 atggagatac tttatactc cattaaataa tttatcatgg agcgataatg tcctgtttca 181200 tttgtttcca tgacatatta caaaatcgat tccgtccaag atgataaaaa catttaccgg 181260 catcataaac acggagttta ttttatatgt ctcgcataaa cattactaaa aaaatatatt 181320 gttctgtttt tctttcacat ctttaattat gaaaaagtaa atcattatga gatggacgag 181380 attgtgagca tcgttcgcga tagtatgtgg tttataccta acgtatttat ggacgacggt 181440 aagaatgaag gtcacgtttc tgtcaacaat gtctgtcata tgtattttac gttctttgat 181500 gtggatacat cgtctcatct gtttaagcta gttattaaac actgcgatct gaataaacga 181560 ggtaactctc cattacattg ctatacgatg aatacacgat ttaatccatc tgtattaaag 181620 atattgttac accacggcat gcgtaacttt gatagcaagg atgaccacta tcaatcgata 181680 acaagatctt tgatatacta acggacacca ttgatgactt tagtaaatca tccgatctat 181740 tgctgtgtta tcttagatat aaattcaatg ggagcttaaa ctattacgtt ctgtacaaag 181800 gatccgaccc taattgcgcc gacgaggatg aactcacttc tcttcattac tactgtaaac 181860 acatatccac gttctacgaa agcaattatt acaagtcaag tcacactaag atgcgagccg 181920 agaagcgatt catctacgcg ataatagatt atggagcaaa cattaacgcg gttacacact 181980 taccttcaac agtataccaa acatagtcct cgtgtggtgt atgctctttt atctcgagga 182040 tacgtaataa tcttgattgt acacccatca tggaacgatt gtgcaacagg tcatattctc 182100 ataatgttac tcaattggca cgaacaaaag gaagaaggac aacatctact ttatctattc 182160 ataaaacata atcaaggata cactctcaat atactacggt atctattaga taggttcgac 182220 attcagaaag acgaatacta taataccgcc tttcaaaatt gtaacaacaa tgttgcctca 182280 tacatcggat acgacatcaa ccttccgact aaagacggta ttcgacttgg tgtttgaaaa 182340 cagaaacatc atatacaagg cggatgttgt gaatgacatc atccaccaca gactgaaagt 182400 atctctacct atgattaaat cgttgttcta caagatgtct ctccctacga cgattactac 182460 gtaaaaaaga tactagccta ctgcctatta agggacgagt cattcgcgga actacatagt 182520 aaattctgtt taaacgagga ctataaaagt gtatttatga aaaatatatc attcgataag 182580 atagattcca tcatcgtgac ataagtcgcc ttaaagagat tcgaatctcc gacaccgacc 182640 tgtatacggt atcacagcta tcttaaagcc atacattcag acagacacat ttcatttccc 182700 atgtacgacg atctcataga acagtgccat ctatcgatgg agcgtaaaag taaactcgtc 182760 gacaaagcac tcaataaatt agagtctacc atcggtcaat ctagactatc gtatttgcct 182820 ccggaaatta tgcgcaatat catctaaaca gtatgttgta cggaaagaac cattacaaat 182880 attatccatg atagaaagaa aatatctata tgattggaga agtaggaaac aggaacaaga 182940 cgacgattac tacattatta aatcatgaag tccgtattat actcgtatat attgtttctc 183000 tcatgtataa taataaacgg aagagatata gcaccgcatg caccatccga tggaaagtgt 183060 aaagacaacg aatacaaacg ccataatttg tgtccgggaa catacgcttc cagattatgc 183120 gatagcaaga ctaacacacg atgtacgccg tgtggttcgg gtaccttcac atctcgcaat 183180 aatcatttac ccgcttgtct aagttgtaac ggaagacgcg atcgtgtaac acgactcaca 183240 atagaatctg tgaatgctct cccggatatt attgtcttct caaaggatca tccggatgca 183300 aggcatgtgt ttcccaaaca aaatgtggaa taggatacgg agtatccgga gacgtcatct 183360 gttctccgtg tggtctcgga acatattctc acaccgtctc ttccgcagat aaatgcgaac 183420 ccgtacccag aaataccttt aactatatcg atgtggaaat taatctgtat cccgtcaacg 183480 acacgtcgtg tactcggacg accactaccg gtctcagcga atccatctca acgtcggaac 183540 taactattac tatgaatcat aaagactgcg atcccgtctt tcgtgatgga tacttctccg 183600 ttcttaataa ggtagcgact tcaggtttct ttacaggaga aaggtgtgca ctctgaattt 183660 cgagattaaa tgcaataaca aagattcttc ctccaaacag ttaacgaaag caaagaatga 183720 tactatcatg ccgcattcgg agacagtaac tctagtgggc gacatctata tactatatag 183780 taataccaat actcaagact acgaaactga tacaatctct tatcatgtgg gtaatgttct 183840 cgatgtcgat agccatatgc ccggtagttg cgatatacat aaactgatca ctaattccaa 183900 acccacccac tttttatagt aagtttttca cccataaata ataaatacaa taattaattt 183960 ctcgtaaaag tagaaaatat attctaattt attgcacggt aaggaagtag aatcataaag 184020 aacagtactc aatcaatagc aattatgaaa caatatacg tactggcatg catgtgcctg 184080 gcggcagctg ctatgcctgc cagtcttcag caatcatcct catcctcctc ctcgtgtacg 184140 gaagaagaaa acaaacatca tatgggaatc gatgttatta tcaaagtcac aaagcaagac 184200 caaacaccga ccaatgataa gatttgccaa tccgtaacgg aaattacaga gtccgagtca 184260 gatccagatc ccgaggtgga atcagaagat gattccacat cagtcgagga tgtagatcct 184320 cctaccactt attactccat catcggtgga ggtctgagaa tgaactttgg attcaccaaa 184380 tgtcctcaga ttaaatccat ctcagaatcc gctgatggaa acacagtgaa tgctagattg 184440 tccagcgtgt cccaggacaa ggtaaggact ctcccgcgat cactcatgaa gaagctcttg 184500 ctatgatcaa agactgtgag gtgtctatcg acatcagatg tagcgaagaa gagaaagaca 184560 gcgacatcaa gacccatcca gtactcgggt ctaacatctc tcataagaaa gtgagttacg 184620 aagatatcat cggttcaacg atcgtcgata caaaatgtgt caagaatcta gagtttagcg 184680 ttcgtatcgg agacatgtgc aaggaatcat ctgaacttga ggtcaaggat ggattcaagt 184740 atgtcgacgg atcggcatct gaaggtgcaa ccgatgatac ttcactcatc gattcaacaa 184800 aactcaaagc gtgtgtctga atcgataact ctattcatct gaaattggat gagtagggtt 184860 aatcgaacga ttcaggcaca ccacgaatta aaaaagtgta ccggacacta tattccggtt 184920 tgcaaaacaa aaatgttctt aactacattc acaaaaagtt acctctcgcg acttcttctt 184980 tttctgtctc aatagtgtga tacgattatg acactattcc tattcctatt cctatttcct 185040 ttcagggtat cacaaaaata ttaaacctct ttctgatggt ctcataaaaa aagttttaca 185100 aaaatatttt tattctcttt ctctctttga tggtctcata aaaaaagttt tacaaaaata 185160 ttttattct ctttctctct ttgatggtct cataaaaaaa gttttacaaa aatattttta 185220 ttctctttct ctctttgatg gtctcataaa aaaagtttta caaaaatatt tttatctct 185280 ttctctcttt gatggtctca taaaaaaagt tttacaaaaa tatttttatt ctctttctct 185340 ctttgatggt ctcataaaaa aagttttaca aaaatatttt tattctcttt ctctctttga 185400 tggtctcata aaaaaagttt tacaaaaata ttttattct ctttctctct ttgatggtct 185460 cataaaaaaa gttttacaaa aatattttta ttctctttct ctctttgatg gtctcataaa 185520 aaaagtttta caaaaatatt tttatctct ttctctcttt gatggtctca taaaaaaagt 185580 tttacaaaaa tatttttatt ctctttctct ctttgatggt ctcataaaaa aagttttaca 185640 aaaatatttt tattctcttt ctctctttga tggtctcata aaaaaagttt tacaaaaata 185700 ttttattct ctttctctct ttgatggtct cataaaaaaa gttttacaaa aatattttta 185760 ttctctttct ctctttgatg gtctcataaa aaaagtttta caaaaatatt tttatctct 185820 ttctctcttt gatggtctca taaaaaaagt tttacaaaaa tatttttatt ctctttctct 185880 ctttgatggt ctcataaaaa aagttttaca aaaatatttt tattctcttt ctctctttga 185940 tggtctcata aaaaaagttt tacaaaaata ttttattct ctttctctct ttgatggtct 186000 cataaaaaaa gttttacaaa aatattttta ttctctttct ctctttgatg gtctcataaa 186060 aaaagtttta caaaaatatt tttatctct ttctctcttt gatggtctca taaaaaatat 186120 taaacctctt tctgatggtg tcactaaaat attttattc tcattctcat tttctctttc 186180 tctcttcaat ggagtcataa aatattttta ttctctttct ctcttcgatg gtctcacaaa 186240 aatattaaac ctctttctga tggtgtcact aaaatatttt tattctcatt ctcatttctct 186300 ctttctctct tcaatggagt cataaaatat tttattctc tttctctctt cgatggtctc 186360 acaaaaatat taaacctctt tctgatggag tcgtaaaaaa gttttatctc tttctctctt 186420 cgatggtttc actaaaatat ttttattct ctttctgatg catcaactat ttcttaaaca 186480 ataacgtcca acaacatata ctcgtcgagc ttatcaacat cccctatgcc catctaggtt 186540 accagacaat tgtatatcat aaaataatgt ttataattta cacgttaaaa tcatataata 186600 aaacgtagat cgtataatat tttttggtat ataaatgatc tagtaaaatc catgtaggggg 186660 atactgctca cattttttct ttggtacaaa atttcacaca agtttttata cagacaaatt 186720 cttgtccata tattttaaaa cattgacttt tgtactaaga aaaatatcta gactaactat 186780 ctctttctct ttctctcttc gatggtctca caaaaatatt aaacctcttt ctgatggagt 186840 cgtaaaaaag ttttatctct ttctctcttc gatggtctca caaaaatatt aaacctcttt 186900 ctgatggagt cgtaaaaaag ttttatctct ttctctcttc gatggtctca caaaaatatt 186960 aaacctcttt ctgatggagt cgtaaaaaag ttttatctct ttctctcttc gatggtctca 187020 caaaaatatt aaacctcttt ctgatggagt cgtaaaaaag ttttatctct ttctctcttc 187080 gatggtctca caaaaatatt aaacctcttt ctgatggagt cgtaaaaaag ttttatctct 187140 ttctctcttc gatggtctca caaaaatatt aaacctcttt ctgatggagt cgtaaaaaag 187200 ttttatctct ttctctcttc gatggtctca caaaaatatt aaacctcttt ctgatggagt 187260 cgtaaaaaag ttttatctct ttctctcttc gatggtctca caaaaatatt aaacctcttt 187320 ctgatggagt cgtaaaaaag ttttatctct ttctctcttc gatggtctca caaaaatatt 187380 aaacctcttt ctgatggagt cgtaaaaaag ttttatctct ttctctcttc gatggtctca 187440 caaaaatatt aaacctcttt ctgatggagt cgtaaaaaag ttttatctct ttctctcttc 187500 gatggtctca caaaaatatt aaacctcttt ctgatggagt cgtaaaaaag ttttatctct 187560 ttctctcttc gatggtctca caaaaatatt aaacctcttt ctgatggagt cgtaaaaaag 187620 ttttatctct ttctctcttc gatggtctca caaaaatatt aaacctcttt ctgatggagt 187680 cgtaaaaaag ttttatctct ttctctcttc gatggtctca caaaaatatt aaacctcttt 187740 ctgatggagt cgtaaaaaag ttttatctct ttctctcttc gatggtctca caaaaatatt 187800 aaacctcttt ctgatggagt cgtaaaaaag ttttatctct ttctctcttc gatggtctca 187860 caaaaatatt aaacctcttt ctgatggagt cgtaaaaaag ttttatctct ttctctcttc 187920 gatggtctca caaaaatatt aaacctcttt ctgatggagt cgtaaaaaag ttttatctct 187980 ttctctcttc gatggtctca caaaaatatt aaacctcttt ctgatggagt cgtaaaaaag 188040 ttttatctct ttctctcttc gatggtctca caaaaatatt aaacctcttt ctgatggagt 188100 cgtaaaaaag ttttatctct ttctctcttc gatggtctca caaaaatatt aaacctcttt 188160 ctgatggtct ctataaagcg atcgatcttt cttacactct agagtttcct acagtcatgg 188220 gtcacacatt tttttctaga cactaaataa aattagtaaa attaaattaa ttataaaatt 188280 atatatataa tttaactaact ttagttagat aaattaataa tatataagtt ttagtacatt 188340 aatattatat tttaaatatt ttatttagtg tctagaaaaa aatgtgtgac ccatgactgt 188400 aggaaactct agagtgtaag aaagatcgat cgctttatag agaccatcag aaaga 188455 <210> 4 <211> 534 <212> DNA <213> artificial sequence <220> <223> Synethic Polynucleotide <400> 4 atgaacggcg gacatattca gttgataatc ggcccccatgt tttcaggtaa aagtacagaa 60 ttaattagac gagttaaacg ttatcaaata gctcaatata aatgcgtgac tataaaatat 120 tctaacgata atagatacgg aacgggacta tggacgcatg ataagaataa ttttgaagca 180 ttggaagcaa ctaaactatg cgatgttttg gaattaatta cagatttctc cgtgataggt 240 atcgatgaag gacagttctt tccagacatt gttgaattct gtgagcgtat ggcaaacgaa 300 ggaaaaatag ttatagtagc cgcactcgat gggacatttc aacgtaaacc gtttaataat 360 attttgaatc ttattccatt atctgaaatg gtggtaaaac taactgctgt gtgtatgaaa 420 tgctttaagg aggcttcctt ttctaaacga ttgggtgagg aaaccgagat aaaaataata 480 ggaggtaatg atatgtatca atcggtgtgt agaaagtgtt acatcgactc ataa 534 <210> 5 <211> 163 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 5 atgaacggcg gacatattca gttgataatc ggcccccatgt tttcaggtaa aagtacagaa 60 ttaattagac gagttaaacg agctcgtcga cggatccgct agcggccgcg gaggtaatga 120 tatgtatcaa tcggtgtgta gaaagtgtta catcgactca taa 163 <210> 6 <211> 175 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 6 gtgaaagcta gagaggggtt tttaaatggt catcggttta gtcatattcg tgtctgtggc 60 ggccgccatc gtcggtgtgt tgtctaacgt attggacatg tttatgtacg tagaagaaaa 120 taatgaagag gatgctagaa tcaaggagga gcaagaacta ctgttgctat attga 175 <210> 7 <211> 100 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 7 gtgaaagcta gagaggaagc ttgagctcga ggatccgcta gcggccgctg aagaggatgc 60 tagaatcaag gaggagcaag aactactgtt gctatattga 100 <210> 8 <211> 657 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 8 atgaattcag tgactgtatc acacgcgcca tatactatta cttatcacga tgattgggaa 60 ccagtaatga gtcaattggt agagttttat aacgaagtag ccagttggct gctacgagac 120 gagacgtcgc ctattcctga taagttcttt atacagttga aacaaccgct tagaaataaa 180 cgagtatgtg tgtgcggtat agatccgtat ccgaaagatg gaactggtgt accgttcgaa 240 tcaccaaatt ttacaaaaaa atcaattaag gagatagctt catctatatc tagattaacc 300 ggagtaattg attataaagg ttataacctt aatataatag acggggttat accctggaat 360 tattacttaa gttgtaaatt aggagaaaca aaaagtcacg cgatctactg ggataagatt 420 tccaagttac tgctgcagca tataactaaa cacgttagtg ttctttattg tttgggtaaa 480 acagatttct cgaatatacg ggccaagtta gaatccccgg taactaccat agtcggatat 540 catccagcgg ctagagaccg ccaattcgag aaagatagat catttgaaat tatcaacgtt 600 ttactggaat tagacaacaa ggcacctata aattgggctc aagggtttat ttattaa 657 <210> 9 <211> 102 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 9 cacaagttcg gatctacggg ttcgatcaca agttcggatc tacgggttac cggtcacaag 60 ttcggatcta cgggtttcac cacaagttcg gatctacggg tt 102 <210> 10 <211> 48 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 10 cacaagttcg gatctacggg tttcaccaca agttcggatc tacgggtt 48 <210> 11 <211> 102 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 11 aaccatacaa cctactacct cacgataacc atacaaccta ctacctcaac cggtaaccat 60 acaacctact acctcatcac aaccatacaa cctactacct ca 102 <210> 12 <211> 3021 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 12 atggatgttc ggtgcattaa ttggtttgaa agtcacggtg aaaacagatt tttatatctg 60 aaatccagat gtcgaaatgg tgagaccgta tttatacgat ttcctcatta cttttattac 120 gtagtgacgg acgaaatata tcagtcattg tctcctcctc catttaatgc gaggccgttg 180 ggaaagatga gaactataga cattgacgag acaataagtt ataatctaga tattaaagat 240 agaaaatgct ccgtcgcaga tatgtggttg atagaagagc caaagaaacg cagcatacaa 300 aatgccacca tggatgaatt tctcaatatt agttggtttt atatttctaa cgggatct 360 ccagacggat gttactcgtt ggacgagcaa tatttgacaa agattaacaa tggatgttat 420 cattgtgacg atccacgtaa ctgtttcgct aaaaaaatac ctagattcga tatcccaaga 480 tcgtacttat ttctagatat agagtgtcac ttcgataaga agtttccttc tgtatttatt 540 aacccaatct cgcatacaag ttactgttat atcgatttaa gtggtaaacg attattgttt 600 acgctcatta atgaagagat gttaacggaa caggaaatac aagaagccgt cgatagagga 660 tgtttgagga tacagtcact aatggaaatg gattacgaac gagaactagt tttatgtctct 720 gaaatagttt tgttacgaat agctaaacaa ttgttggaac taacgttcga ctatgtcgtt 780 acctttaacg gacataactt tgatctgaga tatattacta atcgtctaga gttattaaca 840 ggagagaaga ttatctttag atctccggac aaaaaggaag ctgtacatct ctgtatttat 900 gagagaaatc agtctagtca taagggagta ggcggcatgg ccaatactac gtttcacgtt 960 aataacaata atggaactat atttttcgat ctatattcat tcattcaaaa atctgaaaaa 1020 ttggattcgt acaaattgga ttctatatcc aagaacgcgt tcagttgcat gggtaaagta 1080 ttaaatagag gagttagaga aatgacgttc atcggtgacg atactacgga cgcgaaaggc 1140 aaagccgctg catttgcaaa ggttttaacc acaggtaatt atgtgactgt tgatgaggat 1200 attatatgta aagtaattcg taaagatatt tgggaaaatg gatttaaagt cgtactatta 1260 tgtcctactt tacctaatga tacatataaa ttatctttcg gaaaggatga cgttgattta 1320 gctcagatgt ataaggatta taatctaaac atagctttag atatggctag atactgtatt 1380 catgatgctt gtttgtgtca gtatttgtgg gagtattatg gagtagaaac aaaaacagac 1440 gcgggtgcgt caacatatgt gcttcctcaa tccatggtat tcgaatatag agcgagtaca 1500 gtcatcaagg gtccactgtt aaagctattg ttggaaacta aaactatctt agttagatca 1560 gaaacaaaac aaaagtttcc ttatgaaggc ggtaaggtat ttgctccaaa acaaaaaatg 1620 tttagtaata atgtattaat ctttgattat aacagtctgt atcctaatgt gtgtatcttt 1680 ggaaatctat ctccggaaac attagtcggt gtcgttgtta gtaccaatag attggaagaa 1740 gaaataaata atcagctctt gcttcagaaa tatccacctc ctagatatat tacggttcat 1800 tgtgaaccta gactaccgaa cctcatctct gaaatagcaa ttttcgatag atcgatagaa 1860 ggaaccattc ctagactatt aagaacattt ttggcagaga gagccagata taaaaagatg 1920 ttaaaacagg ctaccagttc aactgaaaag gccatctatg attccatgca atatacgtac 1980 aagatagtag ccaactcagt atatggtctg atgggattta gaaatagtgc tctatactca 2040 tacgcttcgg ctaagagttg cacatccata ggacgtagaa tgatcttgta tctagaatcg 2100 gtactaaatg gagcagagtt atctaacggt atgttacggt ttgccaatcc attaagtaat 2160 ccattttata tggacgatag agatattaat ccgattgtga aaacatcgtt gcctatagat 2220 tacagatttc gttttcgtag cgtgtatgga gataccgact ccgtgtttac agagatagac 2280 agtcaagatg tagataagtc catagaaata gcaaaggagt tagaacgact gattaataat 2340 agagtattgt ttaataattt taaaatagag tttgaggcgg tatataagaa tctgattatg 2400 caatcgaaga agaaatatac aacgatgaaa tactcggcat cgtcgaattc aaaatctgta 2460 cctgagagaa ttaataaagg tactagtgaa actagaagag atgtttccaa gtttcataag 2520 aatatgatta agacatacaa gaccagactg tctgagatgt tgtctgaagg acggatgaat 2580 tctaatcagg tatgtataga tattctccgt tctttagaaa cagatttacg atccgaattt 2640 gatagtagat cgtctcctct agaattattt atgttgagtc gaatgcatca ctcaaattat 2700 aaatccgcag ataaccctaa tatgtatttg gttactgaat ataataaaaa taatccagaa 2760 actatagaac ttggagaacg atattatttt gcatatattt gtccggctaa tgtaccatgg 2820 accaaaaaac ttgtaaatat taaaacatat gaaacaatta tcgatagaag ttttaaactc 2880 ggcagtgatc aaagaatatt ttacgaagtt tactttaaac gattgacgtc cgaaatagtc 2940 aatctattgg ataataaagt tttatgcatc tcattctttg aaagaatgtt tggttcaaaa 3000 cctacatttt acgaagcata a 3021 <210> 13 <211> 1932 <212> DNA <213> Homo sapiens <400> 13 atggaggccg tggagaccgg ggaacggccc accttcggag cctgggacta cggggtcttt 60 gccctcatgc tcctggtgtc cactggcatc gggctgtggg tcgggctggc tcggggcggg 120 cagcgcagcg ctgaggactt cttcaccggg ggccggcgcc tggcggccct gcccgtgggc 180 ctgtcgctgt ctgccagctt catgtcggcc gtgcaggtgc tgggcgtgcc gtcggaggcc 240 tatcgctatg gcctcaagtt cctctggatg tgcctgggcc agcttctgaa ctcggtcctc 300 accgccctgc tcttcatgcc cgtcttctac cgcctgggcc tcaccagcac ctacgagtac 360 ctggagatgc gcttcagccg cgcagtgcgg ctctgcggga ctttgcagta cattgtagcc 420 acgatgctgt acaccggcat cgtaatctac gcaccggccc tcatcctgaa ccaagtgacc 480 gggctggaca tctgggcgtc gctcctgtcc accggaatta tctgcacctt ctacacggct 540 gtgggcggca tgaaggctgt ggtctggact gatgtgttcc aggtcgtggt gatgctaagt 600 ggcttctggg ttgtcctggc acgcggtgtc atgcttgtgg gcgggccccg ccaggtgctc 660 acgctggccc agaaccactc ccggatcaac ctcatggact ttaaccctga cccgaggagc 720 cgctatacat tctggacttt tgtggtgggt ggcacgttgg tgtggctctc catgtatggc 780 gtgaaccagg cgcaggtgca gcgctacgtg gcttgccgca cagagaagca ggccaagctg 840 gccctgctca tcaaccaggt cggcctgttc ctgatcgtgt ccagcgctgc ctgctgtggc 900 atcgtcatgt ttgtgttcta cactgactgc gaccctctcc tcctggggcg catctctgcc 960 ccagaccagt acatgcctct gctggtgctg gacatcttcg aagatctgcc tggagtcccc 1020 gggcttttcc tggcctgtgc ttacagtggc accctcagca cagcatccac cagcatcaat 1080 gctatggctg cagtcactgt agaagacctc atcaaacctc ggctgcggag cctggcaccc 1140 aggaaactcg tgattatctc caaggggctc tcactcatct acggatcggc ctgtctcacc 1200 gtggcagccc tgtcctcact gctcggagga ggtgtccttc agggctcctt caccgtcatg 1260 ggagtcatca gcggccccct gctgggagcc ttcatcttgg gaatgttcct gccggcctgc 1320 aacacaccgg gcgtcctcgc gggactaggc gcgggcttgg cgctgtcgct gtgggtggcc 1380 ttgggcgcca cgctgtaccc acccagcgag cagaccatga gggtcctgcc atcgtcggct 1440 gcccgctgcg tggctctctc agtcaacgcc tctggcctcc tggacccggc tctcctccct 1500 gctaacgact ccagcagggc ccccagctca ggaatggacg ccagccgacc cgccttagct 1560 gacagcttct atgccatctc ctatctctat tacggtgccc tgggcacgct gaccactgtg 1620 ctgtgcggag ccctcatcag ctgcctgaca ggccccacca agcgcagcac cctggccccg 1680 ggattgttgt ggtggggacct cgcacggcag acagcatcag tggcccccaa ggaagaagtg 1740 gccatcctgg atgacaactt ggtcaagggt cctgaagaac tccccactgg aaacaagaag 1800 ccccctggct tcctgcccac caatgaggat cgtctgtttt tcttggggca gaaggagctg 1860 gagggggctg gctcttggac cccctgtgtt ggacatgatg gtggtcgaga ccagcaggag 1920 acaaacctct ga 1932 <210> 14 <211> 717 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 14 atggtgagca agggcgagga gctgttcacc ggggtggtgc ccatcctggt cgagctggac 60 ggcgacgtaa acggccacaa gttcagcgtg tccggcgagg gcgagggcga tgccacctac 120 ggcaagctga ccctgaagtt catctgcacc accggcaagc tgcccgtgcc ctggcccacc 180 ctcgtgacca ccttgaccta cggcgtgcag tgcttcgccc gctaccccga ccacatgaag 240 cagcacgact tcttcaagtc cgccatgccc gaaggctacg tccaggagcg caccatcttc 300 ttcaaggacg acggcaacta caagacccgc gccgaggtga agttcgaggg cgacaccctg 360 gtgaaccgca tcgagctgaa gggcatcgac ttcaaggagg acggcaacat cctggggcac 420 aagctggagt acaactacaa cagccacaag gtctatatca ccgccgacaa gcagaagaac 480 ggcatcaagg tgaacttcaa gacccgccac aacatcgagg acggcagcgt gcagctcgcc 540 gaccactacc agcagaacac ccccatcggc gacggccccg tgctgctgcc cgacaaccac 600 tacctgagca cccagtccgc cctgagcaaa gaccccaacg agaagcgcga tcacatggtc 660 ctgctggagt tcgtgaccgc cgccgggatc actctcggca tggacgagct gtactga 717 <210> 15 <211> 1653 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 15 atggaagatg ccaaaaacat taagaagggc ccagcgccat tctacccact cgaagacggg 60 accgccggcg agcagctgca caaagccatg aagcgctacg ccctggtgcc cggcaccatc 120 gcctttaccg acgcacatat cgaggtggac attacctacg ccgagtactt cgagatgagc 180 gttcggctgg cagaagctat gaagcgctat gggctgaata caaaccatcg gatcgtggtg 240 tgcagcgaga atagcttgca gttcttcatg cccgtgttgg gtgccctgtt catcggtgtg 300 gctgtggccc cagctaacga catctacaac gagcgcgagc tgctgaacag catgggcatc 360 agccagccca ccgtcgtatt cgtgagcaag aaagggctgc aaaagatcct caacgtgcaa 420 aagaagctac cgatcataca aaagatcatc atcatggata gcaagaccga ctaccagggc 480 ttccaaagca tgtacacctt cgtgacttcc catttgccac ccggcttcaa cgagtacgac 540 ttcgtgcccg agagcttcga ccgggacaaa accatcgccc tgatcatgaa cagtagtggc 600 agtaccggat tgcccaaggg cgtagcccta ccgcaccgca ccgcttgtgt ccgattcagt 660 catgcccgcg accccatctt cggcaaccag atcatccccg acaccgctat cctcagcgtg 720 gtgccatttc accacggctt cggcatgttc accacgctgg gctacttgat ctgcggcttt 780 cgggtcgtgc tcatgtaccg cttcgaggag gagctattct tgcgcagctt gcaagactat 840 aagattcaat ctgccctgct ggtgcccaca ctatttagct tcttcgctaa gagcactctc 900 atcgacaagt acgacctaag caacttgcac gagatcgcca gcggcggggc gccgctcagc 960 aaggaggtag gtgaggccgt ggccaaacgc ttccacctac caggcatccg ccagggctac 1020 ggcctgacag aaacaaccag cgccattctg atcaccccccg aaggggacga caagcctggc 1080 gcagtaggca aggtggtgcc cttcttcgag gctaaggtgg tggacttgga caccggtaag 1140 acactgggtg tgaaccagcg cggcgagctg tgcgtccgtg gccccatgat catgagcggc 1200 tacgttaaca accccgaggc tacaaacgct ctcatcgaca aggacggctg gctgcacagc 1260 ggcgacatcg cctactggga cgaggacgag cacttcttca tcgtggaccg gctgaagagc 1320 ctgatcaaat acaagggcta ccaggtagcc ccagccgaac tggagagcat cctgctgcaa 1380 caccccaaca tcttcgacgc cggggtcgcc ggcctgcccg acgacgatgc cggcgagctg 1440 cccgccgcag tcgtcgtgct ggaacacggt aaaaccatga ccgagaagga gatcgtggac 1500 tatgtggcca gccaggttac aaccgccaag aagctgcgcg gtggtgttgt gttcgtggac 1560 gaggtgccta aaggactgac cggcaagttg gacgcccgca agatccgcga gattctcatt 1620 aaggccaaga agggcggcaa gatcgccgtg tga 1653 <210> 16 <211> 711 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 16 atggtgagca agggcgagga ggataacatg gccatcatca aggagttcat gcgcttcaag 60 gtgcacatgg agggctccgt gaacggccac gagttcgaga tcgagggcga gggcgagggc 120 cgcccctacg agggcaccca gaccgccaag ctgaaggtga ccaagggtgg ccccctgccc 180 ttcgcctggg acatcctgtc ccctcagttc atgtacggct ccaaggccta cgtgaagcac 240 cccgccgaca tccccgacta cttgaagctg tccttccccg agggcttcaa gtgggagcgc 300 gtgatgaact tcgaggacgg cggcgtggtg accgtgaccc aggactcctc cctgcaggac 360 ggcgagttca tctacaaggt gaagctgcgc ggcaccaact tcccctccga cggccccgta 420 atgcagaaga agaccatggg ctgggaggcc tcctccgagc ggatgtaccc cgaggacggc 480 gccctgaagg gcgagatcaa gcagaggctg aagctgaagg acggcggcca ctacgacgct 540 gaggtcaaga ccacctacaa ggccaagaag cccgtgcagc tgcccggcgc ctacaacgtc 600 aacatcaagt tggacatcac ctcccacaac gaggactaca ccatcgtgga acagtacgaa 660 cgcgccgagg gccgccactc caccggcggc atggacgagc tgtacaagtg a 711 <210> 17 <211> 813 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 17 atggaaacgg atacattgct tttgtgggta cttctgctct gggtgccggg aagtacagga 60 gacgaggttc aactcgtcga atcaggcgga ggacttgtcc agccgggggg ttctctgcgg 120 ctgagttgtg cagcttcagg attcacattc tcagactcat ggatacattg ggtgcggcaa 180 gcacctgggaa aagggctgga atgggtggct tggataagtc cgtacggagg gagtacttat 240 tacgcggaca gtgtaaaggg caggttcacg attagtgccg acacgagtaa gaataccgcc 300 tatctgcaaa tgaacagttt gcgagcggag gacacagcag tatattattg cgctagacgg 360 cattggccgg gaggcttcga ttattgggga cagggtactc tcgttacggt gagctcaggt 420 ggaggaggga gtgggggtgg cggctccggc ggtggtggtt cagacattca gatgacccag 480 tccccgagct ctctctccgc gtctgtgggt gatcgagtaa ccatcacttg tagagcaagc 540 caagacgtgt caacagccgt agcgtggtac caacagaagc ctgggaaggc tcccaagctc 600 ctgatatatt ctgcaagttt cttgtatagt ggtgtgccca gtaggttttc aggaagcgga 660 tctggtactg acttcacact tactatttca tccttgcaac ctgaggactt cgcaacctat 720 tattgccagc aatacttgta ccaccccgca acttttggcc agggtaccaa ggtagagatc 780 aaacgggact ataaagacga cgatgataag taa 813 <210> 18 <211> 70 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 18 aaaaattgaa aataaataca aaggttcttg agggttgtgt taaattgaaa gcgagaaata 60 atcataaata 70 <210> 19 <211> 34 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 19 aaaaattgaa aaactagcgt ctttttttgc tcga 34 <210> 20 <211> 39 <212> DNA <213> artificial sequence <220> <223> Synthetic Polynucleotide <400> 20 tagtagaatt tcattttgtt tttttctatg ctataaata 39 <210> 21 <211> 37 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 21 gcgcatatga tctatggatt accatggatg acaactc 37 <210> 22 <211> 28 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 22 cgtttaactc gtctaattaa ttctgtac 28 <210> 23 <211> 98 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 23 caggtaaaag tacagaatta attagacgag ttaaacgagc tcgtcgacgg atccgctagc 60 ggccgcggag gtaatgatat gtatcaatcg gtgtgtag 98 <210> 24 <211> 38 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 24 cggaattcgt aattacttag taaatccgcc gtactagg 38 <210> 25 <211> 41 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 25 gcgcatatgt agaagaattg ataaatatga aaccttttaa g 41 <210> 26 <211> 29 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 26 cctctctagc tttcacttaa actgtatcg 29 <210> 27 <211> 100 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 27 gaataatcga tacagtttaa gtgaaagcta gagaggaagc ttgagctcga ggatccgcta 60 gcggccgctg aagaggatgc tagaatcaag gaggagcaag 100 <210> 28 <211> 38 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 28 gcggaattct ccgggcagtg actttgtagc tctcccag 38 <210> 29 <211> 40 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 29 gcgcatatgc acgcgccata tactattact tatcacgatg 40 <210> 30 <211> 33 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 30 ttaataaata aacccttgag cccaatttat agg 33 <210> 31 <211> 163 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 31 cctataaatt gggctcaagg gtttatttat taacacaagt tcggatctac gggttcgatc 60 acaagttcgg atctacgggt taccggtcac aagttcggat ctacgggttt caccacaagt 120 tcggatctac gggtttgctt tagtgaaatt ttaacttgtg ttc 163 <210> 32 <211> 34 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 32 gcggaattcc tagtacctac aacccgaaga gttg 34 <210> 33 <211> 40 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 33 gcgcatatgc acgcgccata tactattact tatcacgatg 40 <210> 34 <211> 33 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 34 ttaataaata aacccttgag cccaatttat agg 33 <210> 35 <211> 163 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 35 cctataaatt gggctcaagg gtttatttat taaaaccata caacctacta cctcacgata 60 accatacaac ctactacctc aaccggtaac catacaacct actacctcat cacaaccata 120 caacctacta cctcatgctt tagtgaaatt ttaacttgtg ttc 163 <210> 36 <211> 34 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 36 gcggaattcc tagtacctac aacccgaaga gttg 34 <210> 37 <211> 43 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 37 gcgggcgccg agtttgaggc ggtatataag aatctgatta tgc 43 <210> 38 <211> 29 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 38 tatgcttcgt aaaatgtagg ttttgaacc 29 <210> 39 <211> 164 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 39 ggttcaaaac ctacatttta cgaagcataa cacaagttcg gatctacggg ttcgatcaca 60 agttcggatc tacgggttac cggtcacaag ttcggatcta cgggtttcac cacaagttcg 120 gatctacggg ttaataattt acaacagttg tacgtcgctc tttg 164 <210> 40 <211> 41 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 40 gcgcaattgc attgctaatg gatcgttctc tggtagatac g 41 <210> 41 <211> 43 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 41 gcgggcgccg agtttgaggc ggtatataag aatctgatta tgc 43 <210> 42 <211> 30 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 42 ttatgcttcg taaaatgtag gttttgaacc 30 <210> 43 <211> 164 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 43 ggttcaaaac ctacatttta cgaagcataa aaccatacaa cctactacct cacgataacc 60 atacaaccta ctacctcaac cggtaaccat acaacctact acctcatcac aaccatacaa 120 cctactacct caaataattt acaacagttg tacgtcgctc tttg 164 <210> 44 <211> 41 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 44 gcgcaattgc attgctaatg gatcgttctc tggtagatac g 41 <210> 45 <211> 75 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 45 gcgaagcttg agctcaaaaa ttgaaaaact agcgtctttt tttgctcgaa gtcgaccacc 60 atggaggccg tggag 75 <210> 46 <211> 50 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 46 gcggatccat aaaaattaat taatcagagg tttgtctcct gctggtctcg 50 <210> 47 <211> 125 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 47 gcgaagcttg agctcaaaaa ttgaaaataa atacaaaggt tcttgagggt tgtgttaaat 60 tgaaagcgag aaataatcat aaatagtcga ccaccatggt gagcaagggc gaggagctgt 120 tcacc 125 <210> 48 <211> 55 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 48 gcgggatcca taaaaattaa ttaatcagta cagctcgtcc atgccgagag tgatc 55 <210> 49 <211> 99 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 49 gcgaagcttg agctctagta gaatttcatt ttgttttttt ctatgctata aatagtcgac 60 caccatgggaa gatgccaaaa acattaagaa gggcccagc 99 <210> 50 <211> 63 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 50 gcgggatcca taaaaattaa ttaatcacac ggcgatcttg ccgcccttct tggccttaat 60 gag 63 <210> 51 <211> 48 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 51 gcggtcgacc accatggaag atgccaaaaa cattaagaag ggcccagc 48 <210> 52 <211> 63 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 52 gcgggatcca taaaaattaa ttaatcacac ggcgatcttg ccgcccttct tggccttaat 60 gag 63 <210> 53 <211> 44 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 53 gcggtcgacc accatggtga gcaagggcga ggaggataac atgg 44 <210> 54 <211> 61 <212> DNA <213> artificial sequence <220> <223> Synthetic polynucleotide <400> 54 gcgggatcca taaaaattaa ttaatcactt gtacagctcg tccatgccgc cggtggagtg 60 g 61

Claims (79)

A chimeric poxvirus comprising a nucleic acid sequence having at least 99% sequence identity to SEQ ID NO: 1, wherein the nucleic acid sequence comprises:
Vaccinia virus strain Brighton, raccoonpox virus strain Herman, rabbitpox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree (Elstree), vaccinia virus strain CL, vaccinia virus strain Lederle-Chorioallantoic, and vaccinia virus strain AS comprising nucleic acid fragments from at least two poxvirus strains selected from the group consisting of human chimeric poxvirus. The chimeric poxvirus of claim 1 , further comprising one or more anti-cancer nucleic acid sequences or nucleic acid sequences encoding detectable moieties. 3. The chimeric poxvirus of claim 2, wherein the one or more anti-cancer nucleic acid sequences form part of a non-essential gene of the chimeric poxvirus. The chimeric poxvirus according to claim 3, wherein the non-essential gene is a thymidine kinase gene. 3. The chimeric poxvirus of claim 2, wherein the one or more anti-cancer nucleic acid sequences independently encode a PD-L1 inhibitor or a sodium iodide symporter. 3. The chimeric poxvirus according to claim 2, wherein each of the one or more anti-cancer nucleic acid sequences is operably linked to a promoter. The chimeric poxvirus according to claim 2, wherein the one or more anticancer nucleic acid sequences independently encode miRNA binding sequences. 3. The chimeric poxvirus according to claim 2, wherein the one or more anti-cancer nucleic acid sequences are a first anti-cancer nucleic acid sequence and a second anti-cancer nucleic acid sequence. The method of claim 1, wherein the nucleic acid fragment is vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, a chimeric poxvirus derived from the vaccinia virus strain Ledle-Pelto and the vaccinia virus strain AS. The method of claim 1, wherein the chimeric poxvirus
(i) vaccinia virus strain Brighton, raccoon fox virus strain Herman, rabbit fox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL, vaccinia virus strain Radle Infecting the cells with two or more poxvirus strains selected from the group consisting of Les-Panthoid and Vaccinia virus strain AS; and
(ii) forming a chimeric poxvirus by allowing the two or more poxvirus strains to replicate
A chimeric poxvirus formed by a method comprising a. 11. The method of claim 10, wherein the cell is vaccinia virus strain Brighton, raccoon fox virus strain Herman, harepox virus strain Utrecht, vaccinia virus strain WR, vaccinia virus strain IHD, vaccinia virus strain Elstree, vaccinia virus strain CL , a chimeric poxvirus that is infected with the vaccinia virus strain Ledle-Elora and the vaccinia virus strain AS. The chimeric poxvirus according to claim 1, wherein the chimeric poxvirus is an oncolytic virus. The chimeric poxvirus according to claim 1, wherein the poxvirus comprises a miRNA binding sequence. An isolated nucleic acid encoding the chimeric poxvirus of claim 1 . A pharmaceutical composition for treating cancer in a subject in need thereof, comprising a therapeutically effective amount of the chimeric poxvirus of claim 1. The chimeric pox virus according to claim 8, wherein the first anti-cancer nucleic acid sequence or the second anti-cancer nucleic acid sequence comprises the sequence of SEQ ID NO: 13 or SEQ ID NO: 17. delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete